N,N,N-Trimethyl-5-[(2,3,5,6-tetra­fluoro­phen­oxy)carbon­yl]pyridin-2-aminium tri­fluoro­methane­sulfonate a precursor for the synthesis of 2,3,5,6-tetra­fluoro­phenyl 6-[¹⁸F]-fluoro­nicotinate

The synthesis, recrystallization, and X-ray deterimination of N,N,N-trimethyl-5-[(2,3,5,6-tetra­fluoro­phen­oxy)carbon­yl]pyridin-2-aminium tri­fluoro­methane­sul­fon­ate (PyTFP-precursor), C₁₅H₁₃F₄N₂O₂⁺·CF₃SO₃⁻, is described. This triflate salt precursor is required for the synthesis of 2,3,5,6-tetra­fluoro­phenyl 6-[¹⁸F]-fluoro­nicotinate ([¹⁸F]FPyTFP), a prosthetic group used to radiolabel peptides for positron emission tomography (PET), as peptides are increasingly being used as PET-imaging probes in nuclear medicine. Radiolabeling of peptides is typically done using a `prosthetic group', a small synthon to which the radioisotope is attached in the first step, followed by attachment to the peptide in the second step. During the synthesis of the PyTFP-precursor, displacement of a Cl atom with tri­methyl­amine gas and anion replacement with a triflate counter-ion is critical, as incomplete replacement would hinder radioisotopic incorporation of nucleophilic fluorine-18 and result in diminished radiochemical yields. The structural determination of the PyTFP-precursor by X-ray crystallography helped confirm the anion exchange of chloride with triflate.

Computing details

Data collection: APEX2 (Bruker, 2012); cell refinement: SAINT (Bruker, 2012); data reduction: SAINT (Bruker, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: SHELXTL (Bruker, 2012); software used to prepare material for publication: SHELXTL (Bruker, 2012).

N,N,N-Trimethyl-5-[(2,3,5,6-tetrafluorophenoxy)carbonyl]pyridin-2-aminium trifluoromethanesulfonate

Crystal data

C15H13F4N2O2^+·CF3O3S^−	F(000) = 968
Mr = 478.34	Dx = 1.668 Mg m^−3
Monoclinic, P21/n	Cu Kα radiation, λ = 1.54178 Å
a = 7.6911 (2) Å	Cell parameters from 9864 reflections
b = 18.4315 (5) Å	θ = 3.3–70.0°
c = 13.5734 (4) Å	µ = 2.47 mm^−1
β = 98.1327 (9)°	T = 210 K
V = 1904.79 (9) Å^3	Irregular, colorless
Z = 4	0.80 × 0.21 × 0.20 mm

Data collection

Bruker APEXII CCD diffractometer	Rint = 0.029
φ and ω scans	θmax = 70.0°, θmin = 4.1°
8360 measured reflections	h = −9→8
3413 independent reflections	k = −20→22
3333 reflections with I > 2σ(I)	l = −15→16

Refinement

Refinement on F^2	56 restraints
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.044	Only H-atom displacement parameters refined
wR(F^2) = 0.123	w = 1/[σ^2(Fo^2) + (0.0525P)^2 + 1.1583P] where P = (Fo^2 + 2Fc^2)/3
S = 1.09	(Δ/σ)max < 0.001
3413 reflections	Δρmax = 0.32 e Å^−3
356 parameters	Δρmin = −0.22 e Å^−3

Special details

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

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
C1	0.3264 (3)	0.38022 (10)	0.30149 (16)	0.0397 (5)
O1	0.4689 (2)	0.36434 (8)	0.37312 (13)	0.0498 (4)
C2	0.3461 (3)	0.38752 (12)	0.20327 (18)	0.0450 (5)
F2	0.50660 (19)	0.38777 (9)	0.17623 (13)	0.0662 (4)
C3	0.1998 (3)	0.39305 (13)	0.13221 (17)	0.0481 (5)
F3	0.2232 (2)	0.39776 (11)	0.03626 (11)	0.0758 (5)
C4	0.0332 (3)	0.39363 (14)	0.15756 (18)	0.0504 (6)
H4	−0.0660	0.3972	0.1087	0.082 (10)*
C5	0.0165 (3)	0.38883 (13)	0.25611 (18)	0.0463 (5)
F5	−0.14365 (19)	0.39032 (10)	0.28456 (13)	0.0712 (5)
C6	0.1605 (3)	0.38171 (11)	0.32809 (16)	0.0408 (5)
F6	0.1398 (2)	0.37541 (8)	0.42392 (10)	0.0583 (4)
C7	0.5671 (3)	0.42035 (11)	0.41525 (16)	0.0365 (4)
O7	0.5380 (2)	0.48161 (8)	0.39221 (14)	0.0603 (5)
C8	0.7118 (3)	0.39312 (10)	0.49015 (15)	0.0347 (4)
C9	0.8301 (3)	0.44349 (11)	0.53723 (17)	0.0433 (5)
H9	0.8117	0.4928	0.5217	0.039 (6)*
N9	0.9679 (2)	0.42530 (9)	0.60308 (14)	0.0438 (4)
C10	0.9901 (3)	0.35577 (11)	0.62420 (15)	0.0350 (4)
N10	1.1516 (2)	0.34048 (9)	0.69614 (12)	0.0375 (4)
C11	0.8823 (3)	0.30115 (12)	0.58190 (18)	0.0470 (5)
H11	0.9053	0.2523	0.5987	0.074 (9)*
C12	0.7391 (3)	0.32086 (11)	0.51388 (17)	0.0453 (5)
H12	0.6611	0.2854	0.4841	0.055 (7)*
C13	1.3104 (3)	0.35168 (13)	0.64484 (17)	0.0459 (5)
H13A	1.3044	0.3194	0.5880	0.054 (7)*
H13B	1.4157	0.3413	0.6909	0.063 (8)*
H13C	1.3135	0.4016	0.6224	0.051 (7)*
C14	1.1603 (3)	0.39094 (15)	0.78401 (18)	0.0532 (6)
H14A	1.1669	0.4407	0.7615	0.054 (7)*
H14B	1.2637	0.3798	0.8312	0.063 (8)*
H14C	1.0560	0.3848	0.8158	0.085 (11)*
C15	1.1562 (3)	0.26358 (13)	0.7340 (2)	0.0526 (6)
H15A	1.0506	0.2539	0.7633	0.068 (8)*
H15B	1.2584	0.2570	0.7840	0.048 (7)*
H15C	1.1625	0.2304	0.6792	0.058 (8)*
S21	0.6944 (7)	0.3137 (4)	0.9015 (4)	0.0440 (3)	0.59
O21	0.5153 (7)	0.2939 (6)	0.8970 (5)	0.0726 (19)	0.59
O22	0.8058 (7)	0.2926 (2)	0.9882 (3)	0.0856 (17)	0.59
O23	0.7633 (6)	0.3025 (3)	0.8106 (3)	0.0833 (14)	0.59
S21B	0.6938 (10)	0.3130 (6)	0.9093 (5)	0.0440 (3)	0.41
O21B	0.5286 (9)	0.2878 (9)	0.8612 (7)	0.071 (3)	0.41
O22B	0.7140 (9)	0.3089 (4)	1.0145 (4)	0.0736 (18)	0.41
O23B	0.8410 (8)	0.2893 (3)	0.8662 (6)	0.093 (3)	0.41
C21	0.6870 (8)	0.4119 (4)	0.9103 (4)	0.0505 (9)	0.59
F21	0.6258 (6)	0.4323 (2)	0.9914 (3)	0.0949 (13)	0.59
F22	0.5898 (6)	0.4414 (2)	0.8335 (4)	0.0962 (17)	0.59
F23	0.8465 (6)	0.4404 (7)	0.9159 (6)	0.0633 (19)	0.59
C21B	0.6919 (11)	0.4105 (6)	0.8878 (6)	0.0505 (9)	0.41
F21B	0.5582 (7)	0.4418 (3)	0.9210 (6)	0.095 (2)	0.41
F22B	0.6801 (10)	0.4247 (3)	0.7920 (4)	0.095 (2)	0.41
F23B	0.8363 (8)	0.4425 (9)	0.9316 (7)	0.063 (3)	0.41

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0426 (11)	0.0309 (9)	0.0422 (12)	−0.0006 (8)	−0.0060 (9)	0.0008 (8)
O1	0.0510 (9)	0.0344 (8)	0.0567 (10)	−0.0016 (6)	−0.0179 (7)	0.0036 (6)
C2	0.0429 (11)	0.0415 (11)	0.0510 (14)	0.0047 (9)	0.0082 (10)	0.0033 (9)
F2	0.0482 (8)	0.0777 (10)	0.0760 (11)	0.0155 (7)	0.0201 (7)	0.0166 (8)
C3	0.0586 (13)	0.0521 (13)	0.0329 (12)	0.0058 (10)	0.0043 (10)	0.0004 (9)
F3	0.0858 (11)	0.1073 (14)	0.0355 (8)	0.0157 (10)	0.0129 (8)	0.0063 (8)
C4	0.0470 (12)	0.0601 (14)	0.0399 (13)	−0.0022 (10)	−0.0085 (10)	−0.0018 (10)
C5	0.0372 (10)	0.0537 (13)	0.0469 (13)	−0.0067 (9)	0.0023 (9)	−0.0028 (9)
F5	0.0409 (7)	0.1062 (13)	0.0671 (11)	−0.0072 (8)	0.0102 (7)	−0.0002 (9)
C6	0.0506 (12)	0.0390 (10)	0.0315 (11)	−0.0039 (9)	0.0008 (9)	−0.0017 (8)
F6	0.0753 (10)	0.0658 (9)	0.0339 (7)	−0.0027 (7)	0.0076 (7)	0.0005 (6)
C7	0.0366 (10)	0.0345 (10)	0.0374 (11)	−0.0009 (8)	0.0017 (8)	0.0004 (8)
O7	0.0614 (10)	0.0356 (8)	0.0742 (13)	−0.0015 (7)	−0.0239 (9)	0.0058 (7)
C8	0.0351 (9)	0.0350 (10)	0.0337 (10)	−0.0003 (7)	0.0037 (8)	0.0001 (7)
C9	0.0416 (11)	0.0329 (10)	0.0520 (13)	−0.0008 (8)	−0.0048 (9)	0.0022 (9)
N9	0.0426 (9)	0.0363 (9)	0.0494 (11)	−0.0035 (7)	−0.0046 (8)	0.0023 (7)
C10	0.0361 (10)	0.0379 (10)	0.0301 (10)	−0.0002 (8)	0.0019 (8)	0.0023 (7)
N10	0.0376 (9)	0.0406 (9)	0.0331 (9)	−0.0008 (7)	0.0011 (7)	0.0031 (7)
C11	0.0594 (13)	0.0322 (10)	0.0444 (13)	−0.0013 (9)	−0.0096 (10)	0.0036 (8)
C12	0.0524 (12)	0.0361 (11)	0.0428 (12)	−0.0062 (9)	−0.0089 (10)	−0.0004 (8)
C13	0.0391 (11)	0.0585 (14)	0.0398 (12)	0.0002 (9)	0.0045 (9)	0.0024 (9)
C14	0.0538 (13)	0.0657 (16)	0.0378 (13)	0.0057 (11)	−0.0021 (11)	−0.0106 (10)
C15	0.0514 (13)	0.0460 (13)	0.0561 (15)	−0.0028 (10)	−0.0073 (11)	0.0172 (11)
S21	0.0450 (3)	0.0412 (3)	0.0433 (7)	−0.0009 (2)	−0.0025 (4)	0.0048 (5)
O21	0.054 (2)	0.064 (4)	0.097 (5)	−0.0159 (19)	0.001 (2)	0.010 (4)
O22	0.106 (4)	0.049 (2)	0.082 (4)	0.001 (2)	−0.053 (3)	0.008 (2)
O23	0.101 (4)	0.077 (3)	0.075 (3)	−0.012 (2)	0.027 (3)	−0.025 (2)
S21B	0.0450 (3)	0.0412 (3)	0.0433 (7)	−0.0009 (2)	−0.0025 (4)	0.0048 (5)
O21B	0.069 (4)	0.052 (3)	0.079 (6)	−0.004 (4)	−0.036 (4)	−0.002 (5)
O22B	0.110 (5)	0.065 (4)	0.040 (3)	−0.020 (3)	−0.008 (3)	0.014 (2)
O23B	0.078 (4)	0.049 (3)	0.166 (8)	0.008 (3)	0.068 (5)	0.000 (4)
C21	0.0482 (14)	0.0450 (13)	0.057 (3)	0.0016 (11)	0.0020 (17)	0.0051 (18)
F21	0.111 (3)	0.074 (2)	0.113 (3)	0.006 (2)	0.062 (3)	−0.021 (2)
F22	0.088 (3)	0.057 (2)	0.125 (4)	−0.006 (2)	−0.051 (3)	0.036 (3)
F23	0.052 (3)	0.053 (3)	0.087 (4)	−0.009 (2)	0.017 (3)	−0.011 (3)
C21B	0.0482 (14)	0.0450 (13)	0.057 (3)	0.0016 (11)	0.0020 (17)	0.0051 (18)
F21B	0.063 (3)	0.060 (3)	0.162 (7)	0.020 (2)	0.010 (4)	−0.013 (4)
F22B	0.138 (6)	0.069 (4)	0.065 (3)	−0.015 (4)	−0.028 (3)	0.032 (3)
F23B	0.070 (5)	0.050 (5)	0.061 (4)	−0.013 (5)	−0.021 (4)	0.014 (3)

Geometric parameters (Å, º)

C1—C2	1.370 (3)	C11—H11	0.9400
C1—C6	1.374 (3)	C12—H12	0.9400
C1—O1	1.390 (3)	C13—H13A	0.9700
O1—C7	1.357 (3)	C13—H13B	0.9700
C2—F2	1.337 (3)	C13—H13C	0.9700
C2—C3	1.378 (3)	C14—H14A	0.9700
C3—F3	1.342 (3)	C14—H14B	0.9700
C3—C4	1.373 (3)	C14—H14C	0.9700
C4—C5	1.365 (3)	C15—H15A	0.9700
C4—H4	0.9400	C15—H15B	0.9700
C5—F5	1.342 (3)	C15—H15C	0.9700
C5—C6	1.376 (3)	S21—O22	1.409 (5)
C6—F6	1.338 (2)	S21—O21	1.418 (5)
C7—O7	1.185 (3)	S21—O23	1.425 (6)
C7—C8	1.485 (3)	S21—C21	1.817 (5)
C8—C12	1.379 (3)	S21B—O23B	1.415 (7)
C8—C9	1.390 (3)	S21B—O22B	1.416 (6)
C9—N9	1.329 (3)	S21B—O21B	1.421 (6)
C9—H9	0.9400	S21B—C21B	1.820 (7)
N9—C10	1.319 (3)	C21—F22	1.311 (5)
C10—C11	1.377 (3)	C21—F21	1.312 (5)
C10—N10	1.494 (3)	C21—F23	1.326 (5)
N10—C13	1.503 (3)	C21B—F21B	1.314 (7)
N10—C14	1.506 (3)	C21B—F22B	1.316 (7)
N10—C15	1.507 (3)	C21B—F23B	1.322 (7)
C11—C12	1.382 (3)
C2—C1—C6	119.2 (2)	C11—C12—H12	120.3
C2—C1—O1	121.1 (2)	N10—C13—H13A	109.5
C6—C1—O1	119.3 (2)	N10—C13—H13B	109.5
C7—O1—C1	118.14 (16)	H13A—C13—H13B	109.5
F2—C2—C1	120.1 (2)	N10—C13—H13C	109.5
F2—C2—C3	120.1 (2)	H13A—C13—H13C	109.5
C1—C2—C3	119.8 (2)	H13B—C13—H13C	109.5
F3—C3—C4	120.0 (2)	N10—C14—H14A	109.5
F3—C3—C2	118.4 (2)	N10—C14—H14B	109.5
C4—C3—C2	121.6 (2)	H14A—C14—H14B	109.5
C5—C4—C3	117.8 (2)	N10—C14—H14C	109.5
C5—C4—H4	121.1	H14A—C14—H14C	109.5
C3—C4—H4	121.1	H14B—C14—H14C	109.5
F5—C5—C4	119.9 (2)	N10—C15—H15A	109.5
F5—C5—C6	118.5 (2)	N10—C15—H15B	109.5
C4—C5—C6	121.6 (2)	H15A—C15—H15B	109.5
F6—C6—C1	119.76 (19)	N10—C15—H15C	109.5
F6—C6—C5	120.3 (2)	H15A—C15—H15C	109.5
C1—C6—C5	120.0 (2)	H15B—C15—H15C	109.5
O7—C7—O1	122.7 (2)	O22—S21—O21	116.0 (5)
O7—C7—C8	126.75 (19)	O22—S21—O23	115.2 (5)
O1—C7—C8	110.50 (16)	O21—S21—O23	113.8 (4)
C12—C8—C9	117.99 (19)	O22—S21—C21	103.9 (4)
C12—C8—C7	124.12 (18)	O21—S21—C21	102.7 (6)
C9—C8—C7	117.87 (18)	O23—S21—C21	102.7 (4)
N9—C9—C8	123.25 (19)	O23B—S21B—O22B	114.9 (6)
N9—C9—H9	118.4	O23B—S21B—O21B	115.1 (6)
C8—C9—H9	118.4	O22B—S21B—O21B	114.2 (6)
C10—N9—C9	117.21 (18)	O23B—S21B—C21B	103.1 (6)
N9—C10—C11	124.6 (2)	O22B—S21B—C21B	102.2 (6)
N9—C10—N10	113.26 (17)	O21B—S21B—C21B	105.2 (9)
C11—C10—N10	122.04 (18)	F22—C21—F21	108.5 (5)
C10—N10—C13	109.04 (15)	F22—C21—F23	107.5 (5)
C10—N10—C14	109.92 (16)	F21—C21—F23	106.1 (5)
C13—N10—C14	109.51 (17)	F22—C21—S21	112.3 (5)
C10—N10—C15	112.17 (16)	F21—C21—S21	111.0 (4)
C13—N10—C15	107.83 (17)	F23—C21—S21	111.1 (7)
C14—N10—C15	108.31 (19)	F21B—C21B—F22B	107.7 (6)
C10—C11—C12	117.5 (2)	F21B—C21B—F23B	107.3 (7)
C10—C11—H11	121.2	F22B—C21B—F23B	107.0 (7)
C12—C11—H11	121.2	F21B—C21B—S21B	111.6 (7)
C8—C12—C11	119.37 (19)	F22B—C21B—S21B	110.7 (6)
C8—C12—H12	120.3	F23B—C21B—S21B	112.5 (9)
C2—C1—O1—C7	87.0 (3)	C9—N9—C10—C11	1.0 (3)
C6—C1—O1—C7	−99.4 (2)	C9—N9—C10—N10	178.00 (18)
C6—C1—C2—F2	178.56 (19)	N9—C10—N10—C13	−71.6 (2)
O1—C1—C2—F2	−7.8 (3)	C11—C10—N10—C13	105.5 (2)
C6—C1—C2—C3	−2.8 (3)	N9—C10—N10—C14	48.5 (2)
O1—C1—C2—C3	170.8 (2)	C11—C10—N10—C14	−134.4 (2)
F2—C2—C3—F3	0.8 (3)	N9—C10—N10—C15	169.06 (19)
C1—C2—C3—F3	−177.9 (2)	C11—C10—N10—C15	−13.8 (3)
F2—C2—C3—C4	−179.4 (2)	N9—C10—C11—C12	−1.2 (4)
C1—C2—C3—C4	2.0 (4)	N10—C10—C11—C12	−178.0 (2)
F3—C3—C4—C5	−179.9 (2)	C9—C8—C12—C11	−0.7 (3)
C2—C3—C4—C5	0.3 (4)	C7—C8—C12—C11	177.4 (2)
C3—C4—C5—F5	179.0 (2)	C10—C11—C12—C8	1.1 (4)
C3—C4—C5—C6	−1.7 (4)	O22—S21—C21—F22	178.9 (5)
C2—C1—C6—F6	−179.29 (19)	O21—S21—C21—F22	−59.9 (6)
O1—C1—C6—F6	6.9 (3)	O23—S21—C21—F22	58.5 (6)
C2—C1—C6—C5	1.5 (3)	O22—S21—C21—F21	−59.5 (6)
O1—C1—C6—C5	−172.33 (19)	O21—S21—C21—F21	61.8 (6)
F5—C5—C6—F6	0.9 (3)	O23—S21—C21—F21	−179.9 (5)
C4—C5—C6—F6	−178.4 (2)	O22—S21—C21—F23	58.4 (6)
F5—C5—C6—C1	−179.8 (2)	O21—S21—C21—F23	179.6 (5)
C4—C5—C6—C1	0.8 (3)	O23—S21—C21—F23	−62.0 (6)
C1—O1—C7—O7	−1.3 (3)	O23B—S21B—C21B—F21B	178.1 (7)
C1—O1—C7—C8	179.57 (17)	O22B—S21B—C21B—F21B	−62.4 (8)
O7—C7—C8—C12	−180.0 (2)	O21B—S21B—C21B—F21B	57.1 (8)
O1—C7—C8—C12	−0.9 (3)	O23B—S21B—C21B—F22B	58.3 (7)
O7—C7—C8—C9	−1.9 (3)	O22B—S21B—C21B—F22B	177.7 (6)
O1—C7—C8—C9	177.14 (19)	O21B—S21B—C21B—F22B	−62.7 (8)
C12—C8—C9—N9	0.5 (3)	O23B—S21B—C21B—F23B	−61.3 (7)
C7—C8—C9—N9	−177.7 (2)	O22B—S21B—C21B—F23B	58.2 (8)
C8—C9—N9—C10	−0.6 (3)	O21B—S21B—C21B—F23B	177.7 (7)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C4—H4···O22^i	0.94	2.63	3.268 (5)	126
C4—H4···O22B^i	0.94	2.56	3.300 (7)	136
C4—H4···F23B^i	0.94	2.55	3.346 (9)	142
C9—H9···F6^ii	0.94	2.55	3.382 (3)	148
C13—H13A···F6^iii	0.97	2.61	3.129 (3)	113
C13—H13A···O22^iv	0.97	2.47	3.402 (5)	161
C13—H13A···O22B^iv	0.97	2.62	3.474 (7)	147
C13—H13B···O21B^iii	0.97	2.55	3.381 (11)	144
C13—H13C···O7^v	0.97	2.46	3.350 (3)	153
C14—H14B···O21^iii	0.97	2.56	3.438 (9)	150
C14—H14B···O21B^iii	0.97	2.64	3.449 (11)	141
C14—H14C···O23B	0.97	2.57	3.400 (6)	143
C14—H14C···F23	0.97	2.47	3.329 (8)	147
C15—H15A···O23	0.97	2.55	3.408 (5)	148
C15—H15A···O23B	0.97	2.37	3.248 (6)	150
C15—H15B···O21^iii	0.97	2.42	3.332 (6)	156
C15—H15B···O21B^iii	0.97	2.26	3.160 (7)	153
C15—H15C···F2^vi	0.97	2.48	3.077 (3)	119
C15—H15C···O22B^iv	0.97	2.44	3.352 (6)	158

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