Methyl (3SR,4RS)-3-benzyl-4-hydroxy-2-oxopyrrolidine-3-carboxyl­ate

In the title compound, C₁₃H₁₅NO₄, the pyrrolidine ring exhibits an envelope conformation with two chiral centres. In the crystal structure, the mol­ecules are linked by N—H...O, O—H...O and C—H...O intermolecular hydrogen bonds to form a three-dimensional network.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.043
• wR factor = 0.128
• Data-to-parameter ratio = 17.5

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry

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S1. Comment

Kainic acid and its derivatives have received much attention for the imminohistochemical, neurochemical and behavioural studies in animal system (Mikulecka et al., 1999; Magnone et al., 2000; Jousselin-Hosaja et al., 2001). On the other hand, it is also a precursor in a long step to synthesize a natural product components such as clausenamide, a liver protecting agent, obtained from the leaves of the plant Clausena lansium (Hartwig et al., 1987). The title compound, (I) (Fig. 1), was obtained as reduced kainic acid in one of the several steps to synthesize the possible derivatives of clausenamide.

The pyrrolidine ring C1/C2/N1/C3/C4 has an envelope conformation since the C2/N1/C3/C4 moiety is almost planar; the C2—N1—C3—C4 torsion angle is −0.68 (14)°. The relative configuration of the chiral centres at atoms C1 and C4 are R and S (or S and R), respectively. The bond lengths and angles of the molecule (Table 1) are in agreement with literature values (Allen et al., 1998). The benzyl C7/C8/C9/C10/C11/C12/C13 and the ester O3/O4/C4/C5/C6 groups are planar and make angle with the pyrrolidine ring of 77.75 (7) and 48.48 (6)°, respectively. The crystal packing is stablized by intermolecular hydrogen bonds, N1—H1A···O4ⁱ, O1—H1B···O2ⁱⁱ and C11—H11A···O2ⁱⁱⁱ (symmetry codes as in Table 2) in a three-dimensional network (Fig. 2).

S2. Experimental

The synthetic approach to the title compound, (I), began with condensation between readily available glycine methyl ester and methyl malonate potassium salt in equimolar amounts to give a diester in 92% yield. Dieckmann cyclization of this diester with sodium/methanol in toluene under reflux gave a β,β-diketoester, 2,4-dioxo-pyrrolidine-3-carboxylic acid methyl ester, in 91% yield. Alkylation of this β,β-diketoester was successfully carried out using benzylbromide in the presence of tetrahydrofuran and tetrabutylammonium flouride (TBAF) to give 3-benzyl-2,4-dioxo-pyrrolidine-3-carboxylic acid methyl ester in 55% yield. Reduction of the alkylated diketoester using NaBH₄/MeOH gave only one isomer of (I) in 65% yield. Suitable crystals of (I) for X-ray investigation were obtained by slow evaporation from an ethyl acetate–petroleum ether solution.

S3. Refinement

After checking their location in the difference Fourier map, all H atoms were included in the refinement in geometrically determined position, and allowed to ride on the parent C, N or O atoms with C—H = 0.97 Å, N—H = 0.89 Å and O—H = 0.85 Å.

Computing details

Data collection: SMART (Siemens, 1996); cell refinement: SAINT (Siemens, 1996); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 1997); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL, PARST (Nardelli, 1995) and PLATON (Spek, 1990).

Figures

	Fig. 1. The molecular structure of the title compound, (I), with ellipsoids shown at the 50% probability level.
	Fig. 2. Packing diagram of (I), viewed down the b axis. The dashed lines denote the N—H···O, O—H···O and C—H···O hydrogen bonds.

Methyl (3SR,4RS)-3-benzyl-4-hydroxy-2-oxopyrrolidine-3-carboxylate

Crystal data

C13H15NO4	Dx = 1.331 Mg m^−3
Mr = 249.26	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pbca	Cell parameters from 5914 reflections
a = 14.7891 (11) Å	θ = 2.6–27.5°
b = 10.8965 (8) Å	µ = 0.10 mm^−1
c = 15.4391 (11) Å	T = 293 K
V = 2488.0 (3) Å^3	Slab, colourless
Z = 8	0.48 × 0.36 × 0.14 mm
F(000) = 1056

Data collection

Bruker SMART APEX CCD area-detector diffractometer	2429 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.019
Graphite monochromator	θmax = 27.5°, θmin = 2.6°
Detector resolution: 83.66 pixels mm^-1	h = −19→12
ω scans	k = −14→13
15920 measured reflections	l = −20→19
2859 independent reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.043	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.128	H-atom parameters constrained
S = 1.06	w = 1/[σ^2(Fo^2) + (0.0755P)^2 + 0.3864P] where P = (Fo^2 + 2Fc^2)/3
2859 reflections	(Δ/σ)max < 0.001
163 parameters	Δρmax = 0.33 e Å^−3
0 restraints	Δρmin = −0.17 e Å^−3

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

	x	y	z	Uiso*/Ueq
N1	0.18617 (7)	0.65338 (9)	0.24409 (7)	0.0395 (2)
H1A	0.2400	0.6340	0.2602	0.047*
O1	0.02326 (7)	0.84984 (8)	0.15162 (7)	0.0537 (3)
H1B	−0.0204	0.8873	0.1710	0.080*
O2	0.12050 (6)	0.46970 (8)	0.27650 (6)	0.0447 (2)
O3	−0.02458 (7)	0.63882 (9)	0.36018 (6)	0.0541 (3)
O4	−0.12282 (6)	0.59980 (14)	0.25449 (8)	0.0682 (3)
C1	0.06201 (8)	0.77869 (10)	0.21727 (8)	0.0384 (3)
H1C	0.0475	0.8154	0.2735	0.046*
C2	0.16499 (8)	0.77190 (11)	0.20736 (8)	0.0420 (3)
H2A	0.1827	0.7762	0.1469	0.050*
H2B	0.1946	0.8374	0.2391	0.050*
C3	0.11673 (7)	0.57630 (11)	0.25124 (7)	0.0328 (2)
C4	0.03200 (7)	0.64140 (10)	0.21759 (7)	0.0328 (3)
C5	−0.04764 (8)	0.62377 (11)	0.27820 (8)	0.0404 (3)
C6	−0.09548 (12)	0.61748 (17)	0.42362 (11)	0.0694 (5)
H6A	−0.0719	0.6308	0.4808	0.104*
H6B	−0.1167	0.5345	0.4187	0.104*
H6C	−0.1447	0.6731	0.4133	0.104*
C7	0.00697 (8)	0.59029 (12)	0.12725 (8)	0.0403 (3)
H7B	−0.0210	0.5105	0.1350	0.048*
H7A	−0.0380	0.6440	0.1017	0.048*
C8	0.08392 (8)	0.57662 (12)	0.06375 (7)	0.0386 (3)
C9	0.13525 (10)	0.47044 (14)	0.06274 (9)	0.0513 (3)
H9A	0.1229	0.4084	0.1024	0.062*
C10	0.20459 (12)	0.45507 (19)	0.00378 (11)	0.0688 (5)
H10A	0.2385	0.3832	0.0043	0.083*
C11	0.22365 (12)	0.5451 (2)	−0.05541 (10)	0.0736 (6)
H11A	0.2704	0.5346	−0.0951	0.088*
C12	0.17306 (14)	0.65126 (18)	−0.05571 (9)	0.0685 (5)
H12A	0.1858	0.7128	−0.0956	0.082*
C13	0.10325 (12)	0.66659 (14)	0.00331 (8)	0.0531 (3)
H13A	0.0690	0.7382	0.0022	0.064*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0219 (5)	0.0471 (5)	0.0496 (6)	−0.0026 (4)	−0.0018 (4)	−0.0004 (4)
O1	0.0561 (6)	0.0449 (5)	0.0600 (6)	0.0152 (4)	0.0057 (5)	0.0066 (4)
O2	0.0370 (5)	0.0430 (5)	0.0540 (5)	0.0015 (3)	−0.0019 (4)	0.0078 (4)
O3	0.0438 (5)	0.0706 (7)	0.0479 (5)	−0.0145 (4)	0.0172 (4)	−0.0111 (4)
O4	0.0232 (5)	0.1057 (10)	0.0755 (7)	−0.0037 (5)	0.0044 (4)	−0.0009 (7)
C1	0.0353 (6)	0.0355 (6)	0.0445 (6)	0.0008 (4)	0.0044 (5)	−0.0033 (4)
C2	0.0350 (6)	0.0429 (6)	0.0482 (6)	−0.0092 (5)	0.0035 (5)	−0.0018 (5)
C3	0.0236 (5)	0.0403 (6)	0.0347 (5)	0.0006 (4)	0.0009 (4)	−0.0028 (4)
C4	0.0211 (5)	0.0376 (6)	0.0397 (6)	0.0001 (4)	0.0015 (4)	−0.0021 (4)
C5	0.0250 (5)	0.0435 (6)	0.0525 (7)	0.0007 (4)	0.0063 (5)	−0.0026 (5)
C6	0.0669 (11)	0.0759 (11)	0.0656 (10)	−0.0140 (8)	0.0375 (8)	−0.0086 (8)
C7	0.0279 (5)	0.0489 (6)	0.0443 (6)	−0.0009 (5)	−0.0042 (4)	−0.0061 (5)
C8	0.0342 (6)	0.0458 (6)	0.0359 (6)	−0.0034 (5)	−0.0055 (4)	−0.0065 (5)
C9	0.0545 (8)	0.0541 (8)	0.0452 (7)	0.0092 (6)	−0.0008 (6)	−0.0076 (6)
C10	0.0567 (9)	0.0944 (12)	0.0554 (9)	0.0218 (9)	−0.0006 (7)	−0.0240 (8)
C11	0.0483 (8)	0.1259 (17)	0.0467 (8)	−0.0147 (10)	0.0084 (6)	−0.0302 (9)
C12	0.0790 (12)	0.0898 (12)	0.0367 (7)	−0.0329 (10)	0.0031 (7)	−0.0043 (7)
C13	0.0643 (9)	0.0552 (8)	0.0399 (6)	−0.0055 (6)	−0.0057 (6)	−0.0005 (5)

Geometric parameters (Å, º)

N1—C3	1.3313 (15)	C6—H6A	0.9600
N1—C2	1.4448 (16)	C6—H6B	0.9600
N1—H1A	0.8600	C6—H6C	0.9600
O1—C1	1.3988 (15)	C7—C8	1.5094 (17)
O1—H1B	0.8200	C7—H7B	0.9700
O2—C3	1.2266 (15)	C7—H7A	0.9700
O3—C5	1.3210 (17)	C8—C13	1.3833 (19)
O3—C6	1.4535 (16)	C8—C9	1.3839 (19)
O4—C5	1.1994 (15)	C9—C10	1.381 (2)
C1—C2	1.5325 (17)	C9—H9A	0.9300
C1—C4	1.5605 (15)	C10—C11	1.370 (3)
C1—H1C	0.9800	C10—H10A	0.9300
C2—H2A	0.9700	C11—C12	1.378 (3)
C2—H2B	0.9700	C11—H11A	0.9300
C3—C4	1.5307 (15)	C12—C13	1.387 (2)
C4—C5	1.5166 (15)	C12—H12A	0.9300
C4—C7	1.5468 (16)	C13—H13A	0.9300
C3—N1—C2	115.41 (10)	O3—C6—H6B	109.5
C3—N1—H1A	122.3	H6A—C6—H6B	109.5
C2—N1—H1A	122.3	O3—C6—H6C	109.5
C1—O1—H1B	109.5	H6A—C6—H6C	109.5
C5—O3—C6	116.07 (12)	H6B—C6—H6C	109.5
O1—C1—C2	111.20 (10)	C8—C7—C4	116.16 (9)
O1—C1—C4	114.65 (10)	C8—C7—H7B	108.2
C2—C1—C4	103.69 (9)	C4—C7—H7B	108.2
O1—C1—H1C	109.0	C8—C7—H7A	108.2
C2—C1—H1C	109.0	C4—C7—H7A	108.2
C4—C1—H1C	109.0	H7B—C7—H7A	107.4
N1—C2—C1	102.68 (9)	C13—C8—C9	118.13 (13)
N1—C2—H2A	111.2	C13—C8—C7	121.60 (12)
C1—C2—H2A	111.2	C9—C8—C7	120.23 (12)
N1—C2—H2B	111.2	C10—C9—C8	121.06 (15)
C1—C2—H2B	111.2	C10—C9—H9A	119.5
H2A—C2—H2B	109.1	C8—C9—H9A	119.5
O2—C3—N1	126.06 (10)	C11—C10—C9	120.38 (16)
O2—C3—C4	125.73 (10)	C11—C10—H10A	119.8
N1—C3—C4	108.12 (10)	C9—C10—H10A	119.8
C5—C4—C3	111.57 (9)	C10—C11—C12	119.45 (15)
C5—C4—C7	108.96 (9)	C10—C11—H11A	120.3
C3—C4—C7	109.58 (9)	C12—C11—H11A	120.3
C5—C4—C1	110.14 (9)	C11—C12—C13	120.20 (15)
C3—C4—C1	102.27 (8)	C11—C12—H12A	119.9
C7—C4—C1	114.23 (10)	C13—C12—H12A	119.9
O4—C5—O3	123.98 (12)	C8—C13—C12	120.77 (15)
O4—C5—C4	124.00 (12)	C8—C13—H13A	119.6
O3—C5—C4	112.02 (10)	C12—C13—H13A	119.6
O3—C6—H6A	109.5
C3—N1—C2—C1	17.87 (14)	C3—C4—C5—O4	−136.14 (14)
O1—C1—C2—N1	−150.18 (10)	C7—C4—C5—O4	−15.02 (17)
C4—C1—C2—N1	−26.48 (12)	C1—C4—C5—O4	111.00 (15)
C2—N1—C3—O2	176.15 (11)	C3—C4—C5—O3	44.32 (13)
C2—N1—C3—C4	−0.68 (14)	C7—C4—C5—O3	165.44 (10)
O2—C3—C4—C5	48.98 (15)	C1—C4—C5—O3	−68.54 (13)
N1—C3—C4—C5	−134.17 (10)	C5—C4—C7—C8	−168.08 (10)
O2—C3—C4—C7	−71.78 (14)	C3—C4—C7—C8	−45.75 (14)
N1—C3—C4—C7	105.07 (11)	C1—C4—C7—C8	68.30 (13)
O2—C3—C4—C1	166.68 (11)	C4—C7—C8—C13	−95.45 (14)
N1—C3—C4—C1	−16.47 (11)	C4—C7—C8—C9	86.89 (14)
O1—C1—C4—C5	−93.73 (12)	C13—C8—C9—C10	0.8 (2)
C2—C1—C4—C5	144.85 (10)	C7—C8—C9—C10	178.49 (13)
O1—C1—C4—C3	147.55 (10)	C8—C9—C10—C11	−0.3 (2)
C2—C1—C4—C3	26.13 (11)	C9—C10—C11—C12	0.0 (2)
O1—C1—C4—C7	29.26 (13)	C10—C11—C12—C13	−0.2 (2)
C2—C1—C4—C7	−92.16 (11)	C9—C8—C13—C12	−1.0 (2)
C6—O3—C5—O4	3.5 (2)	C7—C8—C13—C12	−178.65 (12)
C6—O3—C5—C4	−176.93 (12)	C11—C12—C13—C8	0.7 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O4^i	0.86	2.08	2.8847 (14)	157
O1—H1B···O2^ii	0.82	1.91	2.7309 (14)	176
C11—H11A···O2^iii	0.93	2.56	3.4747 (19)	169

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