(3aS,7aS)-5-[(S)-3,3,3-Trifluoro-2-meth-oxy-2-phenyl-propano-yl]-2,3,4,5,6,7-hexa-hydro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one monohydrate.

rac-Benzyl 3-oxohexa-hydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxyl-ate was separated by chiral chromatography, and one of the enanti-omers ([α](22) (D) = +10°) was hydrogenated in the presence of Pd/C in methanol, producing octa-hydro-3H-pyrrolo[3,4-c]pyridin-3-one. The latter was reacted with (2R)-3,3,3-trifluoro-2-meth-oxy-2-phenyl-propanoyl chloride [(R)-(-)-Mosher acid chloride], giving rise to the title compound, C(17)H(19)F(3)N(2)O(3)·H(2)O. The present structure established the absolute configuration of the pyrrolopiperidine fragment based on the known configuration of the (R)-Mosher acid chloride. The piperidine ring has a somewhat distorted chair conformation and is cis-fused with the five-membered envelope-shaped ring; the plane of the exocyclic amide bond is approximately orthogonal to the plane of the phenyl ring, making a dihedral angle of 82.31 (3)°. The water mol-ecule acts as an acceptor to the proton of the amino group in an N-H⋯O inter-action, and as a double proton donor in O-H⋯O hydrogen bonds, generating infinite bands along the a axis.

Related literature

For the structures of compounds with a similar bicyclic fragment, see: Kim et al. (2007 ▶); Arnott et al. (2006 ▶); Altomare et al. (1995 ▶). For the general synthesis method, see: von Dob­eneck & Hansen (1972 ▶).

Experimental

Crystal data

C17H19F3N2O3·H2O

M = 374.36

Orthorhombic,

a = 8.4870 (4) Å

b = 13.7152 (7) Å

c = 14.9113 (7) Å

V = 1735.69 (15) Å3

Z = 4

Mo Kα radiation

μ = 0.12 mm−1

T = 150 K

0.36 × 0.25 × 0.13 mm

Data collection

Bruker APEXII CCD diffractometer

Absorption correction: multi-scan (SADABS; Bruker, 2001 ▶) T min = 0.957, T max = 0.984

23008 measured reflections

4020 independent reflections

3738 reflections with I > 2σ(I)

R int = 0.034

Refinement

R[F 2 > 2σ(F 2)] = 0.030

wR(F 2) = 0.070

S = 1.02

4020 reflections

248 parameters

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.22 e Å−3

Δρmin = −0.19 e Å−3

Absolute structure: Flack (1983 ▶), 1537 Friedel pairs

Flack parameter: 0.0 (5)

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809053331/kp2243sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809053331/kp2243Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C17H19F3N2O3·H2O	F(000) = 784
Mr = 374.36	Dx = 1.433 Mg m−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 7669 reflections
a = 8.4870 (4) Å	θ = 2.7–27.4°
b = 13.7152 (7) Å	µ = 0.12 mm−1
c = 14.9113 (7) Å	T = 150 K
V = 1735.69 (15) Å3	Block, colourless
Z = 4	0.36 × 0.25 × 0.13 mm

Bruker APEX CCD diffractometer	4020 independent reflections
Radiation source: fine-focus sealed tube	3738 reflections with I > 2σ(I)
graphite	Rint = 0.034
φ and ω scans	θmax = 28.4°, θmin = 2.0°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −11→10
Tmin = 0.957, Tmax = 0.984	k = −17→18
23008 measured reflections	l = −19→18

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.030	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.070	w = 1/[σ2(Fo2) + (0.0343P)2 + 0.299P] where P = (Fo2 + 2Fc2)/3
S = 1.02	(Δ/σ)max = 0.001
4020 reflections	Δρmax = 0.22 e Å−3
248 parameters	Δρmin = −0.19 e Å−3
0 restraints	Absolute structure: Flack (1983), 1537 Friedel pairs
Primary atom site location: structure-invariant direct methods	Flack parameter: 0.0 (5)

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.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

	x	y	z	Uiso*/Ueq
C1	0.46490 (18)	0.72722 (9)	0.80771 (10)	0.0226 (3)
C2	0.43300 (15)	0.68038 (10)	0.71644 (9)	0.0201 (3)
H2	0.4493	0.7315	0.6695	0.024*
C3	0.56770 (15)	0.60584 (10)	0.70764 (10)	0.0216 (3)
H3	0.5959	0.5953	0.6433	0.026*
C4	0.70183 (16)	0.65726 (11)	0.75757 (10)	0.0255 (3)
H4A	0.7755	0.6096	0.7846	0.031*
H4B	0.7612	0.7012	0.7172	0.031*
C5	0.26691 (16)	0.64039 (10)	0.70513 (9)	0.0201 (3)
H5A	0.1896	0.6895	0.7259	0.024*
H5B	0.2466	0.6274	0.6409	0.024*
C6	0.36089 (16)	0.47410 (9)	0.73187 (9)	0.0202 (3)
H6A	0.3522	0.4596	0.6670	0.024*
H6B	0.3380	0.4136	0.7656	0.024*
C7	0.52719 (16)	0.50895 (9)	0.75338 (10)	0.0217 (3)
H7A	0.6036	0.4587	0.7339	0.026*
H7B	0.5378	0.5167	0.8191	0.026*
C8	0.13686 (15)	0.54710 (9)	0.82186 (9)	0.0164 (2)
C9	0.12702 (15)	0.45319 (9)	0.87997 (9)	0.0170 (3)
C10	0.27529 (15)	0.44736 (9)	0.93844 (9)	0.0180 (3)
C11	0.33668 (16)	0.53289 (10)	0.97544 (9)	0.0210 (3)
H11	0.2841	0.5932	0.9660	0.025*
C12	0.47440 (17)	0.53028 (10)	1.02599 (9)	0.0236 (3)
H12	0.5161	0.5887	1.0507	0.028*
C13	0.55050 (16)	0.44225 (10)	1.04025 (10)	0.0245 (3)
H13	0.6450	0.4404	1.0744	0.029*
C14	0.48909 (16)	0.35704 (10)	1.00488 (10)	0.0245 (3)
H14	0.5409	0.2967	1.0155	0.029*
C15	0.35139 (16)	0.35918 (9)	0.95366 (9)	0.0204 (3)
H15	0.3099	0.3006	0.9293	0.025*
C16	−0.01874 (16)	0.45986 (9)	0.94228 (9)	0.0211 (3)
C17	0.00234 (19)	0.36490 (10)	0.75741 (10)	0.0276 (3)
H17A	−0.1051	0.3590	0.7809	0.041*
H17B	0.0251	0.3095	0.7180	0.041*
H17C	0.0119	0.4258	0.7234	0.041*
N1	0.61752 (15)	0.71226 (9)	0.82667 (9)	0.0264 (3)
N2	0.24673 (13)	0.55010 (8)	0.75654 (7)	0.0180 (2)
O1	0.36798 (13)	0.77208 (7)	0.85314 (7)	0.0301 (2)
O2	0.04938 (11)	0.61587 (6)	0.83902 (6)	0.0208 (2)
O3	0.11272 (11)	0.36562 (6)	0.83085 (6)	0.0201 (2)
O1W	0.36093 (13)	0.76305 (8)	1.04178 (8)	0.0273 (2)
F1	−0.00782 (10)	0.52989 (5)	1.00457 (5)	0.02504 (18)
F2	−0.03398 (10)	0.37511 (6)	0.98714 (6)	0.0283 (2)
F3	−0.15420 (9)	0.47343 (6)	0.89841 (6)	0.02748 (19)
H1O	0.359 (3)	0.7767 (16)	0.9843 (17)	0.059 (7)*
H2O	0.424 (3)	0.8062 (16)	1.0675 (14)	0.052 (6)*
H1N	0.665 (2)	0.7341 (13)	0.8794 (13)	0.037 (5)*

	U11	U22	U33	U12	U13	U23
C1	0.0274 (7)	0.0175 (6)	0.0230 (7)	−0.0043 (6)	−0.0012 (6)	0.0047 (5)
C2	0.0194 (6)	0.0223 (6)	0.0188 (7)	−0.0023 (5)	0.0006 (5)	0.0046 (5)
C3	0.0174 (6)	0.0292 (7)	0.0181 (7)	−0.0013 (6)	0.0009 (5)	0.0011 (5)
C4	0.0188 (6)	0.0302 (7)	0.0276 (8)	−0.0047 (6)	−0.0033 (5)	0.0056 (6)
C5	0.0195 (6)	0.0225 (6)	0.0183 (7)	−0.0003 (5)	−0.0010 (5)	0.0053 (5)
C6	0.0203 (6)	0.0201 (6)	0.0202 (7)	0.0014 (6)	0.0035 (5)	−0.0028 (5)
C7	0.0194 (7)	0.0225 (6)	0.0231 (7)	0.0030 (5)	0.0017 (5)	−0.0009 (5)
C8	0.0156 (6)	0.0182 (6)	0.0155 (6)	−0.0018 (5)	−0.0023 (5)	0.0001 (5)
C9	0.0185 (6)	0.0159 (5)	0.0166 (7)	−0.0001 (5)	0.0017 (5)	−0.0004 (5)
C10	0.0184 (6)	0.0206 (6)	0.0150 (7)	0.0014 (5)	0.0016 (5)	0.0023 (5)
C11	0.0246 (7)	0.0191 (6)	0.0194 (7)	0.0024 (6)	−0.0010 (5)	0.0001 (5)
C12	0.0256 (7)	0.0252 (6)	0.0199 (7)	−0.0031 (6)	−0.0012 (5)	−0.0013 (5)
C13	0.0181 (6)	0.0326 (7)	0.0229 (8)	0.0013 (6)	−0.0019 (6)	0.0034 (6)
C14	0.0221 (7)	0.0239 (6)	0.0275 (8)	0.0058 (6)	0.0004 (6)	0.0031 (5)
C15	0.0215 (6)	0.0177 (6)	0.0221 (7)	0.0004 (5)	0.0027 (6)	0.0008 (5)
C16	0.0220 (6)	0.0204 (6)	0.0210 (7)	0.0006 (6)	0.0035 (5)	0.0023 (5)
C17	0.0303 (7)	0.0235 (6)	0.0290 (8)	−0.0063 (6)	−0.0092 (6)	−0.0017 (6)
N1	0.0286 (6)	0.0264 (6)	0.0241 (7)	−0.0067 (5)	−0.0068 (5)	−0.0001 (5)
N2	0.0174 (5)	0.0188 (5)	0.0177 (6)	−0.0010 (5)	0.0009 (4)	0.0003 (4)
O1	0.0373 (6)	0.0251 (5)	0.0280 (6)	−0.0004 (5)	0.0005 (5)	−0.0024 (4)
O2	0.0187 (4)	0.0200 (4)	0.0238 (5)	0.0030 (4)	0.0021 (4)	0.0028 (4)
O3	0.0211 (5)	0.0182 (4)	0.0211 (5)	−0.0020 (4)	−0.0017 (4)	−0.0023 (4)
O1W	0.0307 (6)	0.0256 (5)	0.0256 (6)	−0.0068 (5)	0.0051 (5)	−0.0049 (4)
F1	0.0294 (4)	0.0237 (4)	0.0220 (4)	0.0044 (3)	0.0064 (3)	−0.0012 (3)
F2	0.0337 (5)	0.0227 (4)	0.0286 (5)	−0.0006 (4)	0.0105 (4)	0.0069 (3)
F3	0.0172 (4)	0.0350 (5)	0.0302 (5)	−0.0007 (4)	0.0029 (3)	0.0035 (4)

C1—O1	1.2305 (18)	C9—O3	1.4120 (15)
C1—N1	1.3416 (19)	C9—C10	1.5330 (18)
C1—C2	1.529 (2)	C9—C16	1.5498 (18)
C2—C5	1.5218 (18)	C10—C15	1.3898 (18)
C2—C3	1.5392 (18)	C10—C11	1.3971 (19)
C2—H2	1.0000	C11—C12	1.3913 (19)
C3—C4	1.5321 (19)	C11—H11	0.9500
C3—C7	1.5328 (19)	C12—C13	1.3857 (19)
C3—H3	1.0000	C12—H12	0.9500
C4—N1	1.464 (2)	C13—C14	1.384 (2)
C4—H4A	0.9900	C13—H13	0.9500
C4—H4B	0.9900	C14—C15	1.3964 (19)
C5—N2	1.4664 (16)	C14—H14	0.9500
C5—H5A	0.9900	C15—H15	0.9500
C5—H5B	0.9900	C16—F3	1.3357 (16)
C6—N2	1.4699 (17)	C16—F1	1.3393 (15)
C6—C7	1.5242 (19)	C16—F2	1.3473 (14)
C6—H6A	0.9900	C17—O3	1.4412 (16)
C6—H6B	0.9900	C17—H17A	0.9800
C7—H7A	0.9900	C17—H17B	0.9800
C7—H7B	0.9900	C17—H17C	0.9800
C8—O2	1.2273 (15)	N1—H1N	0.933 (19)
C8—N2	1.3490 (17)	O1W—H1O	0.88 (2)
C8—C9	1.5546 (17)	O1W—H2O	0.88 (2)
O1—C1—N1	127.29 (14)	O3—C9—C16	107.02 (10)
O1—C1—C2	125.57 (13)	C10—C9—C16	108.50 (10)
N1—C1—C2	107.12 (13)	O3—C9—C8	114.85 (10)
C5—C2—C1	114.46 (12)	C10—C9—C8	108.42 (10)
C5—C2—C3	116.05 (11)	C16—C9—C8	109.16 (10)
C1—C2—C3	102.91 (11)	C15—C10—C11	119.53 (12)
C5—C2—H2	107.7	C15—C10—C9	121.31 (12)
C1—C2—H2	107.7	C11—C10—C9	119.14 (11)
C3—C2—H2	107.7	C12—C11—C10	120.38 (12)
C4—C3—C7	110.46 (12)	C12—C11—H11	119.8
C4—C3—C2	101.82 (11)	C10—C11—H11	119.8
C7—C3—C2	111.79 (11)	C13—C12—C11	119.80 (12)
C4—C3—H3	110.8	C13—C12—H12	120.1
C7—C3—H3	110.8	C11—C12—H12	120.1
C2—C3—H3	110.8	C14—C13—C12	120.12 (13)
N1—C4—C3	102.48 (11)	C14—C13—H13	119.9
N1—C4—H4A	111.3	C12—C13—H13	119.9
C3—C4—H4A	111.3	C13—C14—C15	120.39 (13)
N1—C4—H4B	111.3	C13—C14—H14	119.8
C3—C4—H4B	111.3	C15—C14—H14	119.8
H4A—C4—H4B	109.2	C10—C15—C14	119.77 (12)
N2—C5—C2	110.77 (11)	C10—C15—H15	120.1
N2—C5—H5A	109.5	C14—C15—H15	120.1
C2—C5—H5A	109.5	F3—C16—F1	107.42 (10)
N2—C5—H5B	109.5	F3—C16—F2	106.30 (10)
C2—C5—H5B	109.5	F1—C16—F2	106.33 (10)
H5A—C5—H5B	108.1	F3—C16—C9	113.68 (11)
N2—C6—C7	109.59 (10)	F1—C16—C9	113.76 (11)
N2—C6—H6A	109.8	F2—C16—C9	108.86 (10)
C7—C6—H6A	109.8	O3—C17—H17A	109.5
N2—C6—H6B	109.8	O3—C17—H17B	109.5
C7—C6—H6B	109.8	H17A—C17—H17B	109.5
H6A—C6—H6B	108.2	O3—C17—H17C	109.5
C6—C7—C3	112.70 (11)	H17A—C17—H17C	109.5
C6—C7—H7A	109.1	H17B—C17—H17C	109.5
C3—C7—H7A	109.1	C1—N1—C4	113.73 (12)
C6—C7—H7B	109.1	C1—N1—H1N	123.0 (12)
C3—C7—H7B	109.1	C4—N1—H1N	123.2 (12)
H7A—C7—H7B	107.8	C8—N2—C5	118.94 (11)
O2—C8—N2	123.04 (12)	C8—N2—C6	127.93 (11)
O2—C8—C9	119.21 (11)	C5—N2—C6	113.02 (10)
N2—C8—C9	117.70 (11)	C9—O3—C17	117.12 (10)
O3—C9—C10	108.74 (10)	H1O—O1W—H2O	107.0 (19)
O1—C1—C2—C5	−33.31 (19)	C10—C11—C12—C13	−0.4 (2)
N1—C1—C2—C5	148.36 (12)	C11—C12—C13—C14	−0.5 (2)
O1—C1—C2—C3	−160.12 (13)	C12—C13—C14—C15	0.8 (2)
N1—C1—C2—C3	21.55 (13)	C11—C10—C15—C14	−0.67 (19)
C5—C2—C3—C4	−158.45 (12)	C9—C10—C15—C14	177.92 (12)
C1—C2—C3—C4	−32.67 (13)	C13—C14—C15—C10	−0.3 (2)
C5—C2—C3—C7	−40.53 (16)	O3—C9—C16—F3	−68.07 (13)
C1—C2—C3—C7	85.25 (13)	C10—C9—C16—F3	174.76 (11)
C7—C3—C4—N1	−86.77 (13)	C8—C9—C16—F3	56.79 (14)
C2—C3—C4—N1	32.10 (14)	O3—C9—C16—F1	168.56 (10)
C1—C2—C5—N2	−73.86 (14)	C10—C9—C16—F1	51.39 (13)
C3—C2—C5—N2	45.83 (16)	C8—C9—C16—F1	−66.59 (13)
N2—C6—C7—C3	−56.07 (15)	O3—C9—C16—F2	50.20 (13)
C4—C3—C7—C6	157.69 (12)	C10—C9—C16—F2	−66.97 (13)
C2—C3—C7—C6	45.08 (15)	C8—C9—C16—F2	175.06 (10)
O2—C8—C9—O3	129.59 (12)	O1—C1—N1—C4	−178.89 (14)
N2—C8—C9—O3	−52.90 (15)	C2—C1—N1—C4	−0.60 (15)
O2—C8—C9—C10	−108.58 (13)	C3—C4—N1—C1	−20.66 (15)
N2—C8—C9—C10	68.93 (14)	O2—C8—N2—C5	1.99 (19)
O2—C8—C9—C16	9.44 (16)	C9—C8—N2—C5	−175.41 (11)
N2—C8—C9—C16	−173.05 (11)	O2—C8—N2—C6	177.85 (12)
O3—C9—C10—C15	−14.71 (16)	C9—C8—N2—C6	0.44 (19)
C16—C9—C10—C15	101.35 (14)	C2—C5—N2—C8	119.23 (13)
C8—C9—C10—C15	−140.21 (12)	C2—C5—N2—C6	−57.22 (14)
O3—C9—C10—C11	163.89 (11)	C7—C6—N2—C8	−113.09 (14)
C16—C9—C10—C11	−80.05 (14)	C7—C6—N2—C5	62.97 (14)
C8—C9—C10—C11	38.39 (15)	C10—C9—O3—C17	−166.32 (11)
C15—C10—C11—C12	1.0 (2)	C16—C9—O3—C17	76.67 (13)
C9—C10—C11—C12	−177.60 (12)	C8—C9—O3—C17	−44.66 (15)

D—H···A	D—H	H···A	D···A	D—H···A
O1W—H1O···O1	0.88 (2)	1.96 (3)	2.8164 (16)	165 (2)
N1—H1N···O1Wi	0.933 (19)	2.037 (19)	2.8687 (17)	147.7 (16)
O1W—H2O···O2i	0.88 (2)	2.06 (2)	2.9111 (15)	162.8 (19)

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1W—H1O⋯O1	0.88 (2)	1.96 (3)	2.8164 (16)	165 (2)
N1—H1N⋯O1Wi	0.933 (19)	2.037 (19)	2.8687 (17)	147.7 (16)
O1W—H2O⋯O2i	0.88 (2)	2.06 (2)	2.9111 (15)	162.8 (19)

Symmetry code: (i) .