(6S)-6-Iso­butyl­piperidine-2,4-dione and (4R,6S)/(4S,6S)-4-hydroxy-6-iso­butyl­piperidin-2-one

The crystal structure of (6S)-6-iso­butyl­piperidine-2,4-dione, C₉H₁₅NO₂, shows that the keto tautomer is favoured in the solid state. The reduction of the keto functionality leads to the corresponding 4-hydroxy-6-iso­butyl­piperidin-2-one, C₉H₁₇NO₂, with an 84:16 cis/trans ratio, containing the 4R,6S and 4S,6S isomers; the ratio of the two isomers was determined by NMR analysis of the reaction mixture. Crystals obtained from the mixture of both isomers have been studied and shown to contain the isomers in a 86:14 ratio. Hence, both X-ray and NMR analyses show that crystallization does not select the major diastereomer formed by the reduction. In both crystal structures, the two independent mol­ecules dimerize through an (8) hydrogen-bond motif between adjacent amide groups.

S1. Comment

As part of a programme to synthesize enantiopure monohydroxylated δ-lactams, we recently introduced 6-substituted-2,4-dioxopiperidine-1-carboxylates as novel chiral adducts for the asymmetric synthesis of 4-hydroxy-6-substituted-2-oxopiperidine-1-carboxylate. In this series, the pseudo-axial orientation of the side chain at the 6-position [resulting from minimization of the allylic A(1,3) strain] is believed to account for the high stereoselectivity observed in the reduction of the 4-oxo group. A variety of reductive agents and conditions have been explored. Treatment of lactam (I), bearing an isobutyl side chain at atom C6, with NaBH₄ in a mixture of CH₂Cl₂ and 10% acetic acid affords the desired 4-hydroxy derivative in 93% yield with a 90:10 cis/trans ratio (Didierjean et al., 2003).

Surprisingly, the attempt to reduce (I) with tetramethylammonium triacetoxyborohydride in a mixture of MeCN and 15% acetic acid resulted exclusively in removal of the Boc (butyloxycarbonyl) protecting group and afforded (6S)-6-isobutyl-2,4-dioxopiperidine, (II), in 84% yield. Subsequent reduction of (II) with NaBH₄ in a mixture of CH₂Cl₂/AcOH (9:1) gave the corresponding 4-hydroxy-6-isobutyl-2-oxopiperidine, in an 84:16 cis/trans ratio; the (4R,6S) and (4S,6S) isomers are denoted (III) and (IV), respectively The overall yield was 62% and the ratio of isomers was determined by NMR analysis of the reaction mixture. The reduction of (II) is driven by torsional effects that favour attack of the hydride reagent across the axial face of the C=O bond. A similar selectivity (85:15 cis/trans) was reported by Davis and co-workers in the reduction of the related enantiopure (R)-6-phenylpiperidine-2,4-dione (Davis et al., 2000). We present here the results of the X-ray crystallographic analyses of (II), (III) and (IV).

Compound (II) crystallizes with two independent molecules, (IIA) and (IIB), in the asymmetric unit in a triclinic cell. A view of the independent molecules with the atom numbering schemes is shown in Fig. 1. A l l bond distances and angles fall in normal limits (Allen et al., 1987) and are in agreement with the geometry of similar piperidine rings (Didierjean et al., 2003; Marin et al., 2002; Thomas et al., 1996; Bocelli & Grenier-Loustalot, 1981). The S configuration of the C atom at the 6-position of the piperidine ring was assumed from the precursor Boc-β-L-Leu-OH compound (Seebach et al., 1996). Both independent molecules, (IIA) and (IIB), reveal that the keto tautomer is favoured over the enol tautomer in the solid state. This preference is evident from the observed C3—C4 and C4—O2 bond distances in (IIA) [C13—C14 and C14—O12 in (IIB)], which are consistent with single and double bonds, respectively (Table 1). Molecules (IIA) and (IIB) show a similar conformation (Table 1). Both independent piperidine rings adopt a twisted-boat conformation, with the isobutyl group in an equatorial orientation. The C3—C4—C5—C6 and C13—C14—C15—C16 torsion angles [−43.9 (4)° and −21.6 (5)°, respectively] reveal that the conformation is more twisted in (IIA) than in (IIB).

X-ray analysis of crystals obtained from the mixture of (III) and (IV) reveals a monoclinic cell, with two independent molecules in the asymmetric unit. In one of two independent molecules, the C atoms at the 4- and 5-positions and the hydroxy group of the piperidine ring are disordered, leading to a mixture of (III) and (IV) in a 0.712 (8):0.288 (8) ratio. No detectable disorder was observed in the other independent molecule, which is the major diastereomer formed by the reduction of (II), i.e. the diastereomer (4R,6S). Thus the asymmetric unit of the crystal consists of a unit-occupancy and a 0.712 (8) occupancy (4R,6S) diastereomer (Figs. 2 and 3), and a 0.288 (8) occupancy (4S,6S) diastereomer (Fig. 4). The (4R,6S):(4S,6S) ratio in the crystals, determined by crystallographic refinement, is thus 1.712:0.288 (or 86:14), in very good agreement with NMR analysis of the reaction mixture. NMR measurements on the dissolved crystals confirmed that a mixture of the (4R,6S) and (4S,6S) isomers was present in the solid state. In the three structures, the hydroxy group at the 4-position and the isobutyl side chain at the 6-position of the piperidine ring assume an equatorial orientation (Table 3). The two structures of (III) have similar piperidine ring conformations, close to half-chair. The C atom at the 5-position is displaced 0.693 (6) Å [0.610 (3) Å] from the mean plane, defined by atoms N1, C2, C3, C4 and C6 (N11, C12, C13, C14 and C16). The six-membered ring of (IV) adopts a sofa conformation, with the C atom at the 4-position displaced 0.70 (2) Å from the mean plane defined by the five other atoms of the ring. The positions of the hydroxy O atoms in the 0.712 (8)-occupancy molecule of (III) and the 0.288 (8)-occupancy molecule of (IV) are separated by? 0.46 (1) Å. Both hydroxy groups are thus involved in the same intermolecular hydrogen bonds (Table 4).

In both structures, a typical amide–amide hydrogen-bond motif (Rychlewska & Warzatis, 2000) is observed, joining the two independent molecules via two intermolecular N—H···O=C hydrogen bonds (Figs. 5 and 6, and Tables 2 and 4). The amide H atoms, which are obviously cis to the amide carbonyl O atom, form an eight-membered ring, leading to the graph-set motif R₂²(8) (Bernstein et al., 1995). Both crystals show a similar molecular packing, which can be described as a regular stacking of bilayers with the isopropyl groups on the surfaces (Figs. 5 and 6). In each bilayer, the hydrogen-bonded independent dimers (Tables 2 and 4) pack together, the packing? involving mainly van der Waals interactions in the crystal of (II). In the crystal of (III)/(IV), a three-dimensional hydrogen-bond network between the dimers is observed, involving the hydroxy and carbonyl groups of the piperidine rings (Table 4 and Fig. 6). It is interesting to note that the crystals of the N-Boc-protected molecules of (II) and (III) show similar stacking of bilayers, with hydrophobic heads on the surface (Didierjean et al., 2003). Nevertheless, the molecular packing mode inside a bilayer is different. Indeed, strong OH···O=C hydrogen bonds lead to infinite chains packed in a parallel fashion, via van der Waals interactions, to form a bilayer.

S2. Experimental

For the preparation of (6S)-6-isobutylpiperidine-2,4-dione, (II), tetramethylammonium triacetoxyborohydride (293 mg, 1.11 mmol) was added to a stirred solution of I (100 mg, 0.37 mmol) in a mixture of acetonitrile and 15% v/v acetic acid at room temperature. After 48 h, the mixture was quenched with water. Acetonitrile was evaporated under reduced pressure and replaced with ethyl acetate, which was extracted using water and brine. The organic layer was dried over Na₂SO₄, filtered and evaporated to afford a residue that was purified by flash chromatography (ethyl acetate) to give pure (II) (53 mg, 84%). Colorless single crystals of (II), suitable for X-ray analysis, were grown from a mixture of dichloromethane and diisopropyl ether (1:3) (m.p. 395–397 K). ¹H NMR (300 MHz, CDCl₃): δ 7.24 (bs, 1H), 3.80–3.65 (m, 1H), 3.32 (d, J = 19.8 Hz, 1H), 3.20 (d, J = 19.8 Hz), 2.68 (dd, J = 16.3, 4.2 Hz, 1H), 2.31 (dd, J = 16.3, 8.8 Hz, 1H), 1.82–1.62 (m, 1H), 1.57–1.27 (m, 2H), 0.90 (d, J = 2.1 Hz, 3H), 0.87 (d, J = 2.1 Hz, 3H); For the preparation of 4-hydroxy-6-isobutylpiperidin-2-one, (III)/(IV), sodium borohydride (67 mg, 1.77 mmol) was added to a stirred solution of (II) (100 mg, 0.59 mmol) in a mixture of dichloromethane and 10% v/v acetic acid at room temperature. After 72 h, the mixture was quenched with water. Dichloromethane was evaporated under reduced pressure and replaced with ethyl acetate, which was extracted using water and brine. The organic layer was dried over Na₂SO₄, filtered and evaporated to afford a residue that was purified by flash chromatography (ethyl acetate–acetic acid, 95:5), giving a 84:16 mixture (63 mg, 62%) of (III) and the corresponding (4S,6S) diastereomer, (IV). Colorless single crystals of (III/IV), suitable for X-ray analysis, were grown from a mixture of dichloromethane and diisopropyl ether (1:3); the ratio between (III) and (IV) changed to 75:25 (determined by NMR); (m.p. 418–420 K). Spectroscopic analysis of the major diastereomer, (III): ¹H NMR (300 MHz, CD₃OD): δ 4.03–3.93 (m, 1H), 3.49–3.40 (m, 1H), 2.61 (ddd, J = 17.2, 5.6, 2.2 Hz, 1H), 2.20–2.11 (m, 2H), 1.79–1.68 (m, 1H), 1.50–1.41 (m, 1H), 1.39–1.22 (m, 2H), 0.94 (d, J = 3.8 Hz, 3H), 0.92 (d, J = 3.8 Hz, 3H).

S3. Refinement

Because of the lack of any significant anomalous dispersion effects, the absolute configuration could not be determined from the diffraction experiment, so Friedel pairs were merged prior to refinement. All H atoms were placed at calculated positions and refined using a riding model, with C—H distances of 0.93–0.97 Å, an N—H distance of 0.88 Å and an O—H distance of 0.82 Å. The U_iso(H) parameters were fixed at 1.2U_eq(C,N) for methyl, methylene and NH groups, and 1.5U_eq(C,O) for methyl and OH groups. In the (III/IV) crystal structure, the distances between Csp3 atoms in the disordered piperidine rings were restrained to 1.50 (2) Å. The C41, O21 and C51 atoms of the 0.288 (8)-occupancy molecule of (IV) were refined isotropically.

Computing details

Data collection: COLLECT (Nonius, 1998) for (II); COLLECT software (Nonius, 1998) for III_IV. Cell refinement: COLLECT for (II); COLLECT software (Nonius, 1998) for III_IV. For both compounds, data reduction: HKL Suite (Otwinoski & Minor, 1997). Program(s) used to solve structure: SIR92 (Altomare et al., 1994) for (II); SIR_92 (Altomare et al., 1994) for III_IV. For both compounds, program(s) used to refine structure: SHELXL97 (Sheldrick, 1997). Molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and WebLab ViewerPro 3.5 (MSI, 1999) for (II); ORTEP-3 for Windows (Farrugia, 1997), WebLab ViewerPro 3.5 (MSI, 1999) for III_IV. Software used to prepare material for publication: WinGX (Farrugia, 1999) for (II); WinGX publication routines (Farrugia, 1999) for III_IV.

Figures

	Fig. 1. A view of the asymmetric unit of (II), with the atom-numbering scheme and 25% probability displacement ellipsoids. H atoms, except those of the NH groups, have been omitted for clarity. The intermolecular hydrogen bonds are marked as dashed lines.
	Fig. 2. A view of the unit-occupancy molecule of (III), with the atom-numbering scheme and 25% probability displacement ellipsoids. H atoms, except those of the hydroxy and NH groups and asymmetric C atoms, have been omitted for clarity.
	Fig. 3. A view of the 0.712 (8)-occupancy molecule of (III), with the atom-numbering scheme and 25% probability displacement ellipsoids. H atoms, except those of the hydroxy and NH groups and asymmetric C atoms, have been omitted for clarity.
	Fig. 4. A view of the 0.288 (8)-occupancy molecule of (IV), with the atom-numbering scheme and 25% probability displacement ellipsoids. H atoms, except those of the hydroxy and NH groups and asymmetric C atoms, have been omitted for clarity.
	Fig. 5. A packing diagram for (II), viewed along the a axis. The intermolecular hydrogen bonds are marked as dashed lines.
	Fig. 6. A packing diagram for (III/IV), viewed along the b axis. The intermolecular hydrogen bonds are marked as dashed lines. The 0.288 (8)-occupancy molecules of (IV) have been omitted for clarity.

(II)

Crystal data

C9H15NO2	Z = 2
Mr = 169.22	F(000) = 184
Triclinic, P1	Dx = 1.16 Mg m^−3
Hall symbol: P 1	Mo Kα radiation, λ = 0.71073 Å
a = 5.0760 (2) Å	Cell parameters from 7698 reflections
b = 10.0760 (4) Å	θ = 2.1–26.3°
c = 10.1210 (5) Å	µ = 0.08 mm^−1
α = 95.691 (1)°	T = 293 K
β = 102.529 (1)°	Prism, colorless
γ = 103.730 (2)°	0.2 × 0.1 × 0.1 mm
V = 484.65 (4) Å^3

Data collection

Nonius KAPPACCD diffractometer	1334 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.040
Graphite monochromator	θmax = 26.3°, θmin = 2.7°
oscillation scans	h = −5→6
7698 measured reflections	k = −12→12
1959 independent reflections	l = −12→12

Refinement

Refinement on F^2	5 restraints
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.043	w = 1/[σ^2(Fo^2) + (0.0747P)^2] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.118	(Δ/σ)max < 0.001
S = 0.94	Δρmax = 0.14 e Å^−3
1959 reflections	Δρmin = −0.14 e Å^−3
217 parameters

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
N1	0.3820 (5)	0.1967 (3)	0.0122 (3)	0.0566 (7)
H1	0.5467	0.2368	0.0631	0.068*
C2	0.2799 (7)	0.0638 (4)	0.0162 (3)	0.0540 (8)
O1	0.4126 (4)	−0.0013 (2)	0.0917 (2)	0.0663 (7)
C3	−0.0112 (8)	−0.0081 (4)	−0.0706 (4)	0.0689 (10)
H3A	−0.0064	−0.0963	−0.1166	0.083*
H3B	−0.1341	−0.0276	−0.0096	0.083*
C4	−0.1391 (8)	0.0665 (4)	−0.1762 (4)	0.0635 (9)
O2	−0.3847 (6)	0.0255 (3)	−0.2350 (3)	0.0910 (9)
C5	0.0532 (8)	0.1930 (4)	−0.2035 (4)	0.0678 (10)
H5A	−0.057	0.2467	−0.254	0.081*
H5B	0.1692	0.1652	−0.2598	0.081*
C6	0.2382 (6)	0.2816 (3)	−0.0717 (4)	0.0563 (9)
H6	0.1198	0.3178	−0.0209	0.068*
C7	0.4524 (7)	0.4033 (4)	−0.0983 (5)	0.0714 (10)
H7A	0.6028	0.4374	−0.0158	0.086*
H7B	0.5322	0.3706	−0.1699	0.086*
C8	0.3369 (9)	0.5230 (5)	−0.1406 (5)	0.0912 (15)
H8	0.1512	0.4846	−0.2034	0.109*
C9	0.5261 (14)	0.6112 (6)	−0.2166 (8)	0.135 (2)
H9A	0.5432	0.5539	−0.2942	0.202*
H9B	0.708	0.6517	−0.1559	0.202*
H9C	0.4455	0.6833	−0.2473	0.202*
C10	0.3047 (15)	0.6091 (6)	−0.0168 (8)	0.138 (2)
H10A	0.2319	0.6843	−0.0451	0.208*
H10B	0.4838	0.6454	0.0475	0.208*
H10C	0.178	0.5524	0.0259	0.208*
N11	0.9458 (5)	0.1279 (3)	0.2813 (3)	0.0531 (7)
H11	0.8104	0.0816	0.2136	0.064*
O11	0.9300 (5)	0.3245 (3)	0.1947 (3)	0.0751 (8)
O12	1.7096 (6)	0.3177 (3)	0.5272 (3)	0.1004 (11)
C17	0.9541 (7)	−0.1015 (4)	0.3292 (4)	0.0624 (9)
H17A	1.0296	−0.1165	0.2505	0.075*
H17B	0.7518	−0.1266	0.2966	0.075*
C18	1.0328 (7)	−0.1992 (4)	0.4273 (4)	0.0687 (10)
H18	1.2374	−0.1717	0.4597	0.082*
C19	0.9189 (13)	−0.1900 (6)	0.5516 (6)	0.1128 (17)
H19A	0.9765	−0.2534	0.6092	0.169*
H19B	0.7182	−0.2133	0.5238	0.169*
H19C	0.9891	−0.0975	0.6013	0.169*
C20	0.9504 (16)	−0.3462 (6)	0.3500 (7)	0.133 (2)
H20A	1.0018	−0.4073	0.4119	0.2*
H20B	1.0455	−0.3492	0.2779	0.2*
H20C	0.7517	−0.3749	0.3113	0.2*
C12	1.0402 (6)	0.2625 (4)	0.2810 (4)	0.0602 (9)
C16	1.0532 (7)	0.0515 (4)	0.3873 (4)	0.0516 (8)
H16	0.9768	0.068	0.4665	0.062*
C15	1.3716 (7)	0.1052 (4)	0.4313 (4)	0.0600 (9)
H15A	1.4398	0.0686	0.5133	0.072*
H15B	1.4487	0.0701	0.3598	0.072*
C14	1.4771 (7)	0.2587 (4)	0.4596 (4)	0.0628 (10)
C13	1.2854 (8)	0.3397 (4)	0.3962 (5)	0.0863 (13)
H13A	1.395	0.4155	0.3625	0.104*
H13B	1.2146	0.38	0.4677	0.104*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0571 (16)	0.0540 (19)	0.0519 (17)	0.0146 (14)	−0.0015 (12)	0.0100 (13)
C2	0.061 (2)	0.054 (2)	0.0434 (18)	0.0160 (17)	0.0051 (15)	0.0105 (16)
O1	0.0718 (15)	0.0600 (16)	0.0614 (16)	0.0210 (12)	−0.0031 (12)	0.0183 (13)
C3	0.067 (2)	0.066 (2)	0.060 (2)	0.0072 (17)	−0.0031 (17)	0.0139 (18)
C4	0.066 (2)	0.068 (2)	0.047 (2)	0.0178 (19)	−0.0010 (18)	0.0061 (17)
O2	0.0667 (17)	0.102 (2)	0.085 (2)	0.0124 (15)	−0.0117 (14)	0.0195 (17)
C5	0.072 (2)	0.072 (2)	0.054 (2)	0.0212 (18)	−0.0006 (16)	0.0195 (17)
C6	0.0567 (19)	0.054 (2)	0.057 (2)	0.0202 (16)	0.0031 (15)	0.0147 (17)
C7	0.067 (2)	0.061 (2)	0.080 (3)	0.0157 (17)	0.0034 (18)	0.0206 (19)
C8	0.081 (3)	0.062 (3)	0.111 (4)	0.009 (2)	−0.013 (2)	0.031 (3)
C9	0.152 (4)	0.085 (4)	0.149 (6)	0.007 (3)	0.009 (4)	0.059 (4)
C10	0.158 (5)	0.088 (4)	0.174 (7)	0.057 (4)	0.030 (4)	0.008 (4)
N11	0.0516 (15)	0.0565 (18)	0.0485 (17)	0.0166 (13)	0.0025 (12)	0.0130 (13)
O11	0.0716 (15)	0.0624 (17)	0.0814 (19)	0.0137 (12)	−0.0042 (13)	0.0268 (14)
O12	0.0732 (18)	0.091 (2)	0.106 (3)	0.0038 (16)	−0.0265 (15)	0.0249 (18)
C17	0.071 (2)	0.063 (2)	0.056 (2)	0.0227 (17)	0.0131 (16)	0.0148 (17)
C18	0.072 (2)	0.061 (2)	0.076 (3)	0.0275 (18)	0.0111 (19)	0.021 (2)
C19	0.159 (4)	0.118 (4)	0.095 (4)	0.059 (3)	0.058 (3)	0.060 (3)
C20	0.203 (6)	0.074 (3)	0.130 (5)	0.056 (4)	0.032 (4)	0.022 (3)
C12	0.0485 (19)	0.059 (2)	0.068 (2)	0.0141 (16)	0.0004 (17)	0.0175 (19)
C16	0.0531 (17)	0.059 (2)	0.0457 (19)	0.0198 (15)	0.0104 (14)	0.0160 (15)
C15	0.0515 (18)	0.073 (2)	0.058 (2)	0.0226 (16)	0.0087 (15)	0.0198 (17)
C14	0.050 (2)	0.072 (3)	0.058 (2)	0.0071 (17)	0.0023 (18)	0.0170 (19)
C13	0.070 (2)	0.062 (2)	0.101 (3)	0.0099 (19)	−0.021 (2)	0.010 (2)

Geometric parameters (Å, º)

C3—C4	1.489 (5)	C10—H10B	0.96
C4—O2	1.210 (4)	C10—H10C	0.96
C13—C14	1.494 (5)	N11—C12	1.328 (5)
C14—O12	1.204 (4)	N11—C16	1.466 (4)
N1—C2	1.325 (4)	N11—H11	0.86
N1—C6	1.469 (4)	O11—C12	1.236 (4)
N1—H1	0.86	C17—C16	1.516 (5)
C2—O1	1.246 (4)	C17—C18	1.524 (5)
C2—C3	1.511 (5)	C17—H17A	0.97
C3—H3A	0.97	C17—H17B	0.97
C3—H3B	0.97	C18—C19	1.497 (6)
C4—C5	1.500 (6)	C18—C20	1.521 (7)
C5—C6	1.510 (5)	C18—H18	0.98
C5—H5A	0.97	C19—H19A	0.96
C5—H5B	0.97	C19—H19B	0.96
C6—C7	1.523 (5)	C19—H19C	0.96
C6—H6	0.98	C20—H20A	0.96
C7—C8	1.520 (6)	C20—H20B	0.96
C7—H7A	0.97	C20—H20C	0.96
C7—H7B	0.97	C12—C13	1.498 (5)
C8—C10	1.513 (8)	C16—C15	1.526 (5)
C8—C9	1.535 (7)	C16—H16	0.98
C8—H8	0.98	C15—C14	1.488 (5)
C9—H9A	0.96	C15—H15A	0.97
C9—H9B	0.96	C15—H15B	0.97
C9—H9C	0.96	C13—H13A	0.97
C10—H10A	0.96	C13—H13B	0.97
C2—N1—C6	125.7 (3)	C12—N11—C16	125.5 (3)
C2—N1—H1	117.2	C12—N11—H11	117.3
C6—N1—H1	117.2	C16—N11—H11	117.3
O1—C2—N1	122.1 (3)	C16—C17—C18	116.1 (3)
O1—C2—C3	119.8 (3)	C16—C17—H17A	108.3
N1—C2—C3	118.1 (3)	C18—C17—H17A	108.3
C4—C3—C2	117.2 (3)	C16—C17—H17B	108.3
C4—C3—H3A	108	C18—C17—H17B	108.3
C2—C3—H3A	108	H17A—C17—H17B	107.4
C4—C3—H3B	108	C19—C18—C20	112.4 (5)
C2—C3—H3B	108	C19—C18—C17	113.5 (3)
H3A—C3—H3B	107.2	C20—C18—C17	109.7 (4)
O2—C4—C3	120.8 (4)	C19—C18—H18	106.9
O2—C4—C5	123.1 (3)	C20—C18—H18	106.9
C3—C4—C5	116.2 (3)	C17—C18—H18	106.9
C4—C5—C6	111.3 (3)	C18—C19—H19A	109.5
C4—C5—H5A	109.4	C18—C19—H19B	109.5
C6—C5—H5A	109.4	H19A—C19—H19B	109.5
C4—C5—H5B	109.4	C18—C19—H19C	109.5
C6—C5—H5B	109.4	H19A—C19—H19C	109.5
H5A—C5—H5B	108	H19B—C19—H19C	109.5
N1—C6—C5	109.6 (3)	C18—C20—H20A	109.5
N1—C6—C7	109.9 (3)	C18—C20—H20B	109.5
C5—C6—C7	111.8 (3)	H20A—C20—H20B	109.5
N1—C6—H6	108.5	C18—C20—H20C	109.5
C5—C6—H6	108.5	H20A—C20—H20C	109.5
C7—C6—H6	108.5	H20B—C20—H20C	109.5
C8—C7—C6	114.7 (3)	O11—C12—N11	123.2 (3)
C8—C7—H7A	108.6	O11—C12—C13	120.4 (4)
C6—C7—H7A	108.6	N11—C12—C13	116.3 (3)
C8—C7—H7B	108.6	N11—C16—C17	108.2 (3)
C6—C7—H7B	108.6	N11—C16—C15	108.6 (3)
H7A—C7—H7B	107.6	C17—C16—C15	112.8 (3)
C10—C8—C7	110.5 (4)	N11—C16—H16	109
C10—C8—C9	111.4 (5)	C17—C16—H16	109
C7—C8—C9	110.2 (4)	C15—C16—H16	109
C10—C8—H8	108.2	C14—C15—C16	114.2 (3)
C7—C8—H8	108.2	C14—C15—H15A	108.7
C9—C8—H8	108.2	C16—C15—H15A	108.7
C8—C9—H9A	109.5	C14—C15—H15B	108.7
C8—C9—H9B	109.5	C16—C15—H15B	108.7
H9A—C9—H9B	109.5	H15A—C15—H15B	107.6
C8—C9—H9C	109.5	O12—C14—C15	122.5 (3)
H9A—C9—H9C	109.5	O12—C14—C13	120.1 (3)
H9B—C9—H9C	109.5	C15—C14—C13	117.3 (3)
C8—C10—H10A	109.5	C14—C13—C12	116.9 (3)
C8—C10—H10B	109.5	C14—C13—H13A	108.1
H10A—C10—H10B	109.5	C12—C13—H13A	108.1
C8—C10—H10C	109.5	C14—C13—H13B	108.1
H10A—C10—H10C	109.5	C12—C13—H13B	108.1
H10B—C10—H10C	109.5	H13A—C13—H13B	107.3
N1—C2—C3—C4	12.6 (5)	C2—C3—C4—O2	−168.9 (4)
C2—C3—C4—C5	11.0 (5)	O2—C4—C5—C6	135.9 (4)
C3—C4—C5—C6	−43.9 (5)	C2—N1—C6—C7	−155.4 (3)
C4—C5—C6—N1	52.7 (4)	N1—C6—C7—C8	−160.3 (3)
C2—N1—C6—C5	−32.1 (5)	C5—C6—C7—C8	77.7 (4)
C6—N1—C2—C3	−1.1 (5)	C6—C7—C8—C10	78.3 (5)
C4—C5—C6—C7	174.8 (3)	C6—C7—C8—C9	−158.2 (4)
N11—C12—C13—C14	27.0 (6)	C16—C17—C18—C19	60.2 (5)
C15—C14—C13—C12	−16.2 (6)	C16—C17—C18—C20	−173.2 (4)
C16—C15—C14—C13	−21.6 (5)	C16—N11—C12—O11	−174.5 (3)
N11—C16—C15—C14	47.2 (4)	C12—N11—C16—C17	−163.0 (3)
C12—N11—C16—C15	−40.1 (4)	C18—C17—C16—N11	−177.0 (3)
C16—N11—C12—C13	3.0 (5)	C18—C17—C16—C15	62.7 (4)
C17—C16—C15—C14	167.2 (3)	C16—C15—C14—O12	160.5 (4)
C6—N1—C2—O1	−178.9 (3)	O12—C14—C13—C12	161.7 (4)
O1—C2—C3—C4	−169.5 (3)	O11—C12—C13—C14	−155.4 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O11	0.86	2.04	2.899 (3)	176
N11—H11···O1	0.86	2.05	2.878 (3)	161

(III_IV)

Crystal data

C9H17NO2	F(000) = 376
Mr = 171.24	Dx = 1.166 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 2173 reflections
a = 12.9121 (6) Å	θ = 1.0–26.4°
b = 5.3871 (3) Å	µ = 0.08 mm^−1
c = 14.8945 (7) Å	T = 100 K
β = 109.692 (2)°	Prism, colorless
V = 975.45 (8) Å^3	0.2 × 0.1 × 0.1 mm
Z = 4

Data collection

Nonius KAPPACCD diffractometer	1760 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.079
Graphite monochromator	θmax = 26.3°, θmin = 2.6°
oscillation scans	h = −16→16
18084 measured reflections	k = −6→6
2196 independent reflections	l = −18→17

Refinement

Refinement on F^2	7 restraints
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.043	w = 1/[σ^2(Fo^2) + (0.0769P)^2 + 0.0386P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.114	(Δ/σ)max = 0.002
S = 1.01	Δρmax = 0.16 e Å^−3
2196 reflections	Δρmin = −0.19 e Å^−3
236 parameters

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
O1	0.67946 (11)	0.6828 (3)	1.04958 (10)	0.0319 (4)
N1	0.68232 (14)	0.7075 (4)	0.89926 (12)	0.0295 (5)
H1	0.7277	0.5802	0.9122	0.035*
C2	0.64628 (17)	0.7824 (5)	0.96856 (15)	0.0291 (6)
O2	0.4449 (4)	1.2792 (11)	0.8307 (4)	0.0404 (11)	0.712 (8)
H2	0.4097	1.2476	0.8675	0.061*	0.712 (8)
C3	0.5635 (2)	0.9892 (5)	0.94855 (17)	0.0379 (6)	0.712 (8)
H3A	0.5883	1.1094	1.0018	0.045*	0.712 (8)
H3B	0.4929	0.9186	0.949	0.045*	0.712 (8)
C4	0.5416 (3)	1.1311 (8)	0.8560 (2)	0.0315 (11)	0.712 (8)
H4	0.6053	1.2451	0.8645	0.038*	0.712 (8)
C5	0.5391 (3)	0.9472 (8)	0.7780 (2)	0.0295 (10)	0.712 (8)
H5A	0.5218	1.0351	0.7163	0.035*	0.712 (8)
H5B	0.4811	0.8216	0.7718	0.035*	0.712 (8)
C6	0.6543 (2)	0.8153 (5)	0.80329 (16)	0.0331 (6)	0.712 (8)
H6	0.7118	0.9371	0.8011	0.04*	0.712 (8)
C7	0.6439 (2)	0.6083 (5)	0.73134 (17)	0.0372 (6)
H7A	0.7047	0.4889	0.7586	0.045*
H7B	0.574	0.5189	0.7218	0.045*
C8	0.6463 (2)	0.6931 (6)	0.63432 (15)	0.0405 (7)
H8	0.5987	0.8437	0.6145	0.049*
C9	0.5981 (3)	0.4876 (7)	0.56153 (19)	0.0618 (9)
H9A	0.603	0.5362	0.4997	0.093*
H9B	0.5208	0.4609	0.5551	0.093*
H9C	0.6395	0.3338	0.5831	0.093*
C10	0.7618 (2)	0.7602 (8)	0.63802 (19)	0.0609 (9)
H10A	0.8096	0.6147	0.6578	0.091*
H10B	0.7901	0.8949	0.684	0.091*
H10C	0.7601	0.8143	0.5747	0.091*
O21	0.4302 (11)	1.203 (2)	0.8175 (9)	0.034 (3)*	0.288 (8)
H21	0.3853	1.1942	0.8472	0.052*	0.288 (8)
C31	0.5635 (2)	0.9892 (5)	0.94855 (17)	0.0379 (6)	0.288 (8)
H31A	0.5108	0.9588	0.9826	0.045*	0.288 (8)
H31B	0.6012	1.149	0.9711	0.045*	0.288 (8)
C41	0.5033 (8)	1.000 (3)	0.8427 (6)	0.035 (2)*	0.288 (8)
H41	0.4605	0.8434	0.8222	0.042*	0.288 (8)
C51	0.5854 (10)	1.025 (2)	0.7890 (7)	0.035 (2)*	0.288 (8)
H51A	0.5447	1.0455	0.7201	0.042*	0.288 (8)
H51B	0.631	1.1755	0.8116	0.042*	0.288 (8)
C61	0.6543 (2)	0.8153 (5)	0.80329 (16)	0.0331 (6)	0.288 (8)
H61	0.7258	0.8926	0.8064	0.04*	0.288 (8)
O11	0.81679 (11)	0.2582 (3)	0.94945 (9)	0.0299 (4)
O12	1.06794 (13)	−0.2869 (4)	1.17635 (11)	0.0353 (4)
H12	1.1077	−0.3	1.1421	0.053*
N11	0.83492 (14)	0.2784 (4)	1.10496 (12)	0.0288 (5)
H11	0.7832	0.3926	1.0901	0.035*
C12	0.85924 (16)	0.1795 (5)	1.03320 (14)	0.0260 (5)
C13	0.93683 (17)	−0.0382 (5)	1.05320 (15)	0.0293 (5)
H13A	0.9836	−0.0246	1.0126	0.035*
H13B	0.8934	−0.1929	1.0353	0.035*
C14	1.01056 (18)	−0.0561 (5)	1.15703 (15)	0.0304 (6)
H14	1.0651	0.0828	1.1718	0.037*
C15	0.94089 (19)	−0.0340 (5)	1.21962 (15)	0.0314 (5)
H15A	0.9876	−0.0562	1.2871	0.038*
H15B	0.8844	−0.1664	1.2031	0.038*
C16	0.88493 (17)	0.2184 (5)	1.20713 (14)	0.0293 (5)
H16	0.9419	0.3467	1.2376	0.035*
C17	0.79473 (18)	0.2343 (5)	1.25201 (15)	0.0331 (6)
H17A	0.7392	0.1044	1.2232	0.04*
H17B	0.7577	0.3973	1.2356	0.04*
C18	0.8344 (2)	0.2037 (6)	1.36104 (16)	0.0407 (7)
H18	0.8738	0.0412	1.3769	0.049*
C19	0.9146 (3)	0.4062 (7)	1.4117 (2)	0.0639 (9)
H19A	0.8802	0.5689	1.3928	0.096*
H19B	0.981	0.3946	1.394	0.096*
H19C	0.9343	0.3857	1.4808	0.096*
C20	0.7355 (3)	0.1922 (9)	1.3941 (2)	0.0708 (11)
H20A	0.7603	0.1601	1.4629	0.106*
H20B	0.6864	0.0585	1.3603	0.106*
H20C	0.6961	0.3508	1.3805	0.106*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0310 (8)	0.0337 (10)	0.0313 (8)	0.0044 (8)	0.0108 (6)	0.0069 (8)
N1	0.0324 (10)	0.0256 (11)	0.0307 (9)	0.0042 (10)	0.0111 (8)	0.0029 (9)
C2	0.0244 (11)	0.0287 (14)	0.0341 (13)	−0.0009 (11)	0.0098 (9)	0.0023 (11)
O2	0.037 (2)	0.042 (3)	0.048 (2)	0.017 (2)	0.0214 (18)	0.019 (2)
C3	0.0400 (13)	0.0397 (16)	0.0373 (13)	0.0115 (14)	0.0174 (10)	0.0073 (13)
C4	0.0275 (19)	0.031 (2)	0.0386 (19)	0.0057 (18)	0.0140 (14)	0.0073 (17)
C5	0.0230 (18)	0.0264 (19)	0.0369 (18)	−0.0010 (17)	0.0070 (14)	0.0055 (16)
C6	0.0406 (13)	0.0266 (13)	0.0315 (12)	0.0016 (12)	0.0112 (10)	0.0029 (11)
C7	0.0395 (13)	0.0292 (14)	0.0374 (13)	0.0042 (12)	0.0056 (10)	−0.0020 (11)
C8	0.0459 (13)	0.0420 (17)	0.0283 (11)	0.0127 (15)	0.0054 (10)	−0.0006 (13)
C9	0.078 (2)	0.060 (2)	0.0373 (15)	0.0108 (19)	0.0059 (13)	−0.0103 (16)
C10	0.0569 (16)	0.091 (3)	0.0349 (13)	0.007 (2)	0.0157 (12)	0.0043 (18)
C31	0.0400 (13)	0.0397 (16)	0.0373 (13)	0.0115 (14)	0.0174 (10)	0.0073 (13)
C61	0.0406 (13)	0.0266 (13)	0.0315 (12)	0.0016 (12)	0.0112 (10)	0.0029 (11)
O11	0.0298 (8)	0.0322 (10)	0.0267 (8)	0.0029 (8)	0.0081 (6)	0.0025 (8)
O12	0.0354 (9)	0.0344 (10)	0.0382 (9)	0.0114 (9)	0.0153 (7)	0.0078 (9)
N11	0.0281 (9)	0.0282 (11)	0.0287 (9)	0.0052 (10)	0.0078 (7)	0.0040 (9)
C12	0.0220 (10)	0.0241 (13)	0.0305 (12)	−0.0036 (11)	0.0071 (8)	−0.0005 (11)
C13	0.0286 (11)	0.0290 (13)	0.0311 (11)	0.0010 (12)	0.0112 (9)	−0.0006 (11)
C14	0.0312 (12)	0.0260 (13)	0.0328 (12)	0.0041 (12)	0.0092 (9)	0.0028 (11)
C15	0.0331 (12)	0.0321 (13)	0.0283 (11)	0.0020 (12)	0.0095 (9)	0.0042 (12)
C16	0.0285 (11)	0.0295 (13)	0.0266 (10)	0.0000 (12)	0.0053 (8)	0.0006 (11)
C17	0.0338 (12)	0.0346 (14)	0.0306 (11)	0.0058 (12)	0.0104 (9)	0.0020 (11)
C18	0.0473 (14)	0.0426 (16)	0.0338 (12)	0.0140 (15)	0.0160 (10)	0.0066 (13)
C19	0.090 (2)	0.055 (2)	0.0366 (15)	0.004 (2)	0.0084 (14)	−0.0063 (15)
C20	0.0694 (19)	0.108 (3)	0.0475 (16)	0.026 (2)	0.0354 (14)	0.019 (2)

Geometric parameters (Å, º)

O1—C2	1.257 (3)	C41—H41	1
N1—C2	1.330 (3)	C51—H51A	0.99
N1—C6	1.471 (3)	C51—H51B	0.99
N1—H1	0.88	O11—C12	1.255 (2)
C2—C3	1.503 (4)	O12—C14	1.426 (3)
O2—C4	1.422 (5)	O12—H12	0.84
O2—H2	0.84	N11—C12	1.323 (3)
C3—C4	1.517 (4)	N11—C16	1.475 (3)
C3—H3A	0.99	N11—H11	0.88
C3—H3B	0.99	C12—C13	1.505 (3)
C4—C5	1.519 (6)	C13—C14	1.522 (3)
C4—H4	1	C13—H13A	0.99
C5—C6	1.575 (4)	C13—H13B	0.99
C5—H5A	0.99	C14—C15	1.503 (3)
C5—H5B	0.99	C14—H14	1
C6—C7	1.521 (3)	C15—C16	1.521 (4)
C6—H6	1	C15—H15A	0.99
C7—C8	1.526 (3)	C15—H15B	0.99
C7—H7A	0.99	C16—C17	1.528 (3)
C7—H7B	0.99	C16—H16	1
C8—C10	1.517 (4)	C17—C18	1.538 (3)
C8—C9	1.528 (4)	C17—H17A	0.99
C8—H8	1	C17—H17B	0.99
C9—H9A	0.98	C18—C20	1.516 (4)
C9—H9B	0.98	C18—C19	1.518 (5)
C9—H9C	0.98	C18—H18	1
C10—H10A	0.98	C19—H19A	0.98
C10—H10B	0.98	C19—H19B	0.98
C10—H10C	0.98	C19—H19C	0.98
O21—C41	1.410 (17)	C20—H20A	0.98
O21—H21	0.84	C20—H20B	0.98
C41—C51	1.533 (13)	C20—H20C	0.98
C2—N1—C6	126.8 (2)	C41—C51—H51A	109.4
C2—N1—H1	116.6	C41—C51—H51B	109.4
C6—N1—H1	116.6	H51A—C51—H51B	108
O1—C2—N1	121.4 (2)	C14—O12—H12	109.5
O1—C2—C3	119.78 (19)	C12—N11—C16	127.2 (2)
N1—C2—C3	118.86 (19)	C12—N11—H11	116.4
C2—C3—C4	117.1 (2)	C16—N11—H11	116.4
C2—C3—H3A	108	O11—C12—N11	121.6 (2)
C4—C3—H3A	108	O11—C12—C13	119.90 (19)
C2—C3—H3B	108	N11—C12—C13	118.50 (18)
C4—C3—H3B	108	C12—C13—C14	113.42 (19)
H3A—C3—H3B	107.3	C12—C13—H13A	108.9
O2—C4—C3	113.7 (3)	C14—C13—H13A	108.9
O2—C4—C5	111.9 (4)	C12—C13—H13B	108.9
C3—C4—C5	108.4 (3)	C14—C13—H13B	108.9
O2—C4—H4	107.5	H13A—C13—H13B	107.7
C3—C4—H4	107.5	O12—C14—C15	108.8 (2)
C5—C4—H4	107.5	O12—C14—C13	111.4 (2)
C4—C5—C6	109.7 (3)	C15—C14—C13	108.98 (18)
C4—C5—H5A	109.7	O12—C14—H14	109.2
C6—C5—H5A	109.7	C15—C14—H14	109.2
C4—C5—H5B	109.7	C13—C14—H14	109.2
C6—C5—H5B	109.7	C14—C15—C16	110.7 (2)
H5A—C5—H5B	108.2	C14—C15—H15A	109.5
N1—C6—C7	109.3 (2)	C16—C15—H15A	109.5
N1—C6—C5	108.3 (2)	C14—C15—H15B	109.5
C7—C6—C5	108.1 (2)	C16—C15—H15B	109.5
N1—C6—H6	110.4	H15A—C15—H15B	108.1
C7—C6—H6	110.4	N11—C16—C15	110.29 (19)
C5—C6—H6	110.4	N11—C16—C17	107.81 (16)
C8—C7—C6	115.0 (2)	C15—C16—C17	113.4 (2)
C8—C7—H7A	108.5	N11—C16—H16	108.4
C6—C7—H7A	108.5	C15—C16—H16	108.4
C8—C7—H7B	108.5	C17—C16—H16	108.4
C6—C7—H7B	108.5	C16—C17—C18	115.09 (18)
H7A—C7—H7B	107.5	C16—C17—H17A	108.5
C10—C8—C7	111.71 (19)	C18—C17—H17A	108.5
C10—C8—C9	111.0 (2)	C16—C17—H17B	108.5
C7—C8—C9	108.8 (3)	C18—C17—H17B	108.5
C10—C8—H8	108.4	H17A—C17—H17B	107.5
C7—C8—H8	108.4	C20—C18—C19	112.1 (3)
C9—C8—H8	108.4	C20—C18—C17	109.3 (2)
C8—C9—H9A	109.5	C19—C18—C17	112.1 (2)
C8—C9—H9B	109.5	C20—C18—H18	107.7
H9A—C9—H9B	109.5	C19—C18—H18	107.7
C8—C9—H9C	109.5	C17—C18—H18	107.7
H9A—C9—H9C	109.5	C18—C19—H19A	109.5
H9B—C9—H9C	109.5	C18—C19—H19B	109.5
C8—C10—H10A	109.5	H19A—C19—H19B	109.5
C8—C10—H10B	109.5	C18—C19—H19C	109.5
H10A—C10—H10B	109.5	H19A—C19—H19C	109.5
C8—C10—H10C	109.5	H19B—C19—H19C	109.5
H10A—C10—H10C	109.5	C18—C20—H20A	109.5
H10B—C10—H10C	109.5	C18—C20—H20B	109.5
C41—O21—H21	109.5	H20A—C20—H20B	109.5
O21—C41—C51	108.2 (10)	C18—C20—H20C	109.5
O21—C41—H41	108.8	H20A—C20—H20C	109.5
C51—C41—H41	108.8	H20B—C20—H20C	109.5
N11—C12—C13—C14	−22.1 (3)	C61—N1—C2—C3	3.6 (4)
C12—C13—C14—C15	49.3 (3)	C2—C31—C41—O21	−175.2 (8)
C13—C14—C15—C16	−62.7 (3)	C2—N1—C61—C7	−142.6 (2)
C14—C15—C16—N11	46.8 (2)	C6—N1—C2—O1	−176.9 (2)
C15—C16—N11—C12	−19.8 (3)	C6—N1—C2—C3	3.6 (4)
C16—N11—C12—C13	7.5 (3)	O1—C2—C3—C4	169.7 (3)
C12—C13—C14—O12	169.41 (19)	O2—C4—C5—C6	172.1 (3)
C14—C15—C16—C17	167.86 (18)	C2—N1—C6—C7	−142.7 (2)
N1—C2—C3—C4	−10.8 (4)	N1—C6—C7—C8	−164.04 (19)
C2—C3—C4—C5	40.1 (4)	C5—C6—C7—C8	78.3 (3)
C3—C4—C5—C6	−61.8 (4)	C6—C7—C8—C10	75.7 (3)
C4—C5—C6—N1	53.9 (4)	C6—C7—C8—C9	−161.5 (2)
C5—C6—N1—C2	−25.1 (4)	C16—N11—C12—O11	−174.7 (2)
C2—C3—C4—O2	165.2 (4)	O11—C12—C13—C14	160.0 (2)
C4—C5—C6—C7	172.2 (3)	O12—C14—C15—C16	175.55 (17)
N1—C2—C31—C41	23.3 (6)	C12—N11—C16—C17	−144.1 (2)
C2—C31—C41—C51	−55 (1)	N11—C16—C17—C18	−173.9 (2)
C31—C41—C51—C61	63 (1)	C15—C16—C17—C18	63.7 (3)
C41—C51—C61—N1	−35 (1)	C16—C17—C18—C20	−173.2 (3)
C51—C61—N1—C2	2.7 (7)	C16—C17—C18—C19	61.9 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O11	0.88	2.05	2.925 (3)	172
N11—H11···O1	0.88	2.01	2.888 (3)	172
O12—H12···O11^i	0.84	1.95	2.769 (2)	164
O2—H2···O1^ii	0.84	1.98	2.821 (5)	177
O21—H21···O1^ii	0.84	1.98	2.797 (14)	163

Symmetry codes: (i) −x+2, y−1/2, −z+2; (ii) −x+1, y+1/2, −z+2.