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Acta Cryst. (2007). E63, o3938    [ doi:10.1107/S1600536807041803 ]

1:1 Cocrystal of (S)-3-(ammoniomethyl)-5-methylhexanoate and (S)-mandelic acid

B. Samas, W. Wang and D. B. Godrej

Abstract top

The title compound, C8H17NO2·C8H8O3, exists as a complex with the base (pregabalin) in the predicted zwitterion form, based on the pKa differences between the acid and base. The asymmetric unit consists of two molecules of each component. The -NH3 group adopts the standard propeller conformation. The structure forms pairs of hydrophobic and hydrophilic interactions along both the a and c axes.

Comment top

The title complex, (I), is an important intermediate in the overall synthesis of pregabalin. Pregabalin, marketed as Lyrica by Pfizer (see http://www.lyrica.com), is an approved drug for the treatment of diabetic nerve and shingle pain amongst others.

Taking advantage of the complex's unusual physio-chemical properties, mandelic acid is used to resolve racemic pregabalin on industrial scale. A crystallization of 1:1 mandelic acid to pregabalin results in the free form. Complex (I) forms only with an excess of mandelic acid.

The complex is resolved by either 1) adding two molar equivalents of the acid or 2) adding a slight excess of mandelic acid combined with an inorganic acid, the method of Pope and Peachy (Pope & Peachey, 1899). The resolved pregabalin–mandelic acid complex is isolated and recrystallized to remove the complexed mandelic acid and recover the free form (Hoekstra et al., 1997; Mulhern, 1996). At ratios of 1:1 pregabalin with mandelic acid, the free form was isolated from both slurries and crystallizations. However, with 1:2 pregabalin:mandelic acid, (I) was isolated under both conditions.

All strong hydrogen bond acceptors and donors are utilized. The ratio of donors to acceptors is 5 to 3. Two extra donating protons donate to the same acceptor; resulting in one hydrogen bond acceptor (delocalized carbonyl) accepting three protons. This is an unusual finding. While there are many examples of carbonyl with three hydrogen bonds, it is unusual for a carboxylate to accept three hydrogen bonds.

Some close contacts between the carboxylate group and protons (D—H···A) on the NH3 group were not hydrogen bonds (e.g. N2—H2B—O8). In these cases, the hydrogen bond angles were very bent and the geometry of the accepting OH group did not appear to favor accepting a hydrogen bond. The closeness of these accepting and donating groups could be a function of the forced propeller NH3 conformation or the opposite charges of carboxylate and NH3 groups.

Related literature top

For related literature, see: Hoekstra et al. (1997); Mulhern (1996); Pope & Peachey (1899).

Experimental top

Attempts to crystallize a suitable diffraction quality crystal took some time. Many of the crystals grown were non-merohedrally twinned at a ratio of 10:1. With careful technique, sheets of crystal could be removed from the twinned crystals. The sheets were high quality single crystals, yet were not of acceptable volume to diffract well. The twinned structures did not refine as well as this untwinned structure. We choose a untwinned crystal and collected for long exposures. The chirality of pregabalin was determined by relative configuration from the fixed chiral center of the mandelic acid.

Refinement top

Friedel pairs were merged in the absence of signifcant anomalous scattering effects. H atoms bound to carbon were positioned geometrically, with C—H distances of 0.95 Å, and refined using a riding model.

Computing details top

Data collection: XSCANS (Siemens, 1991); cell refinement: XSCANS (Siemens, 1991); data reduction: SAINT-Plus (Bruker, 2003); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP (Sheldrick, 1996); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997).

Figures top
[Figure 1] Fig. 1. ORTEP diagram. Atomic displacement ellipsoids are at 30% probability, hydrogen atoms are given as arbritary radii.
[Figure 2] Fig. 2. Hydrophilic/hydrophobic interactions visible by looking down the a axis. Protons involoved in hydrogen bonding are shown in green.
(S)-3-(ammoniomethyl)-5-methylhexanoate–(S)-mandelic acid (1/1) top
Crystal data top
C8H17NO2·C8H8O3F000 = 672
Mr = 311.37Dx = 1.198 Mg m−3
Monoclinic, P21Mo Kα radiation
λ = 0.71073 Å
Hall symbol: P 2ybCell parameters from 815 reflections
a = 6.2922 (13) Åθ = 3.0–18.4º
b = 27.423 (6) ŵ = 0.09 mm−1
c = 10.009 (2) ÅT = 296 (2) K
β = 90.84 (3)ºPlate, colourless
V = 1726.9 (6) Å30.22 × 0.11 × 0.05 mm
Z = 4
Data collection top
Bruker SMART APEX2 CCD
diffractometer		4159 independent reflections
Radiation source: fine-focus sealed tube2488 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.096
T = 296(2) Kθmax = 28.2º
φ and ω scansθmin = 1.5º
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)		h = −8→8
Tmin = 0.956, Tmax = 0.996k = −36→36
38738 measured reflectionsl = −13→13
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.059  w = 1/[σ2(Fo2) + (0.0842P)2]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.148(Δ/σ)max < 0.001
S = 0.92Δρmax = 0.58 e Å−3
4159 reflectionsΔρmin = −0.21 e Å−3
407 parametersExtinction correction: none
1 restraintAbsolute structure: Flack (1983), with 3849 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: ?
Secondary atom site location: difference Fourier map
Crystal data top
C8H17NO2·C8H8O3V = 1726.9 (6) Å3
Mr = 311.37Z = 4
Monoclinic, P21Mo Kα
a = 6.2922 (13) ŵ = 0.09 mm−1
b = 27.423 (6) ÅT = 296 (2) K
c = 10.009 (2) Å0.22 × 0.11 × 0.05 mm
β = 90.84 (3)º
Data collection top
Bruker SMART APEX2 CCD
diffractometer		4159 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)		2488 reflections with I > 2σ(I)
Tmin = 0.956, Tmax = 0.996Rint = 0.096
38738 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.059H-atom parameters constrained
wR(F2) = 0.148Δρmax = 0.58 e Å−3
S = 0.92Δρmin = −0.21 e Å−3
4159 reflectionsAbsolute structure: Flack (1983), with 3849 Friedel pairs
407 parametersFlack parameter: ?
1 restraint
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.1574 (8)0.34998 (17)0.3221 (4)0.0322 (10)
H10.01600.33980.35110.039*
O70.8185 (5)0.41070 (11)1.0833 (3)0.0319 (7)
O40.2132 (5)0.38722 (12)0.5318 (3)0.0329 (7)
H40.23840.41260.57230.049*
O100.3202 (5)0.46157 (11)0.6609 (3)0.0312 (7)
O10.7161 (5)0.48461 (11)0.2123 (3)0.0314 (7)
H1A0.73780.45910.17210.047*
O90.0740 (5)0.44728 (11)0.8170 (3)0.0309 (7)
C20.7324 (7)0.47677 (17)0.3419 (4)0.0260 (10)
O80.5720 (5)0.42446 (11)0.9265 (3)0.0306 (7)
O20.7914 (5)0.43870 (12)0.3910 (3)0.0316 (7)
N10.2478 (6)0.46247 (13)1.0859 (3)0.0280 (8)
H1B0.35200.45321.03230.042*
H1C0.12540.44981.05680.042*
H1D0.27540.45201.16850.042*
O50.2925 (5)0.43222 (12)0.3533 (3)0.0337 (7)
N20.7488 (6)0.40986 (13)0.6580 (3)0.0300 (9)
H2A0.84320.41930.71980.045*
H2B0.62200.42230.67670.045*
H2C0.78910.42030.57810.045*
C30.7354 (7)0.35569 (17)0.6570 (4)0.0305 (10)
H3A0.87560.34230.64170.037*
H3B0.64290.34540.58400.037*
O30.6535 (6)0.51155 (13)0.5613 (3)0.0378 (8)
H30.53720.49930.57600.057*
C40.2282 (7)0.39496 (17)0.4026 (4)0.0276 (10)
O60.1506 (6)0.35999 (13)0.1826 (3)0.0449 (9)
H60.04030.37450.16360.067*
C50.2322 (7)0.51655 (17)1.0857 (4)0.0309 (10)
H5A0.37170.53031.10380.037*
H5B0.13900.52671.15680.037*
C60.7182 (7)0.39958 (15)0.9754 (4)0.0245 (9)
C70.6390 (7)0.27979 (16)0.7801 (4)0.0289 (10)
H7A0.78300.26710.78080.035*
H7B0.57410.27110.69490.035*
C80.1473 (7)0.53650 (16)0.9530 (4)0.0278 (10)
H80.00230.52430.93900.033*
C90.2197 (7)0.47262 (16)0.7684 (4)0.0248 (9)
C100.6498 (7)0.33543 (16)0.7893 (4)0.0263 (9)
H100.50470.34770.79990.032*
C110.6697 (7)0.52180 (16)0.4222 (4)0.0280 (9)
H110.53290.53410.38840.034*
C120.2836 (7)0.52008 (16)0.8331 (4)0.0274 (9)
H12A0.27790.54550.76560.033*
H12B0.43020.51730.86340.033*
C130.7829 (7)0.35234 (16)0.9105 (4)0.0271 (9)
H13A0.77870.32690.97770.032*
H13B0.92930.35550.88290.032*
C140.8380 (7)0.56137 (16)0.4073 (4)0.0273 (9)
C150.3129 (7)0.30842 (18)0.3442 (4)0.0317 (10)
C160.1376 (8)0.59252 (15)0.9640 (4)0.0299 (10)
H16A0.28190.60500.96700.036*
H16B0.07210.60091.04810.036*
C171.0324 (7)0.55679 (19)0.4744 (4)0.0365 (11)
H171.06170.52890.52450.044*
C180.7999 (8)0.60233 (18)0.3304 (5)0.0367 (11)
H180.67150.60600.28420.044*
C190.5152 (8)0.31030 (19)0.2856 (5)0.0384 (11)
H190.55570.33790.23850.046*
C200.0145 (8)0.61907 (18)0.8497 (5)0.0399 (12)
H200.08880.61280.76600.048*
C210.5157 (9)0.25445 (18)0.8912 (5)0.0428 (12)
H210.59050.26100.97590.051*
C221.1817 (8)0.59351 (18)0.4668 (4)0.0376 (12)
H221.31000.59020.51320.045*
C230.2604 (9)0.26761 (19)0.4164 (5)0.0402 (12)
H230.12880.26630.45740.048*
C240.5162 (10)0.19979 (18)0.8693 (6)0.0511 (15)
H24A0.66010.18820.86840.077*
H24B0.44760.19240.78540.077*
H24C0.44110.18410.94030.077*
C250.9565 (9)0.6381 (2)0.3230 (5)0.0482 (14)
H250.93220.66520.26920.058*
C260.5924 (11)0.2306 (2)0.3709 (5)0.0581 (16)
H260.68590.20450.37960.070*
C270.0182 (11)0.6735 (2)0.8746 (6)0.0572 (15)
H27A−0.05470.68070.95590.086*
H27B−0.05110.69000.80140.086*
H27C0.16280.68450.88220.086*
C281.1461 (9)0.63459 (19)0.3927 (5)0.0438 (13)
H281.24660.65940.38950.053*
C290.6519 (9)0.2718 (2)0.2975 (5)0.0416 (12)
H290.78400.27290.25710.050*
C30−0.2121 (10)0.6011 (2)0.8329 (7)0.0638 (18)
H30A−0.28910.62260.77410.096*
H30B−0.27930.60040.91840.096*
H30C−0.21150.56880.79570.096*
C310.3978 (11)0.2285 (2)0.4298 (5)0.0567 (16)
H310.35830.20110.47830.068*
C320.2890 (11)0.2730 (2)0.9043 (9)0.079 (3)
H32A0.20920.26510.82480.118*
H32B0.29070.30770.91650.118*
H32C0.22410.25780.98000.118*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.033 (3)0.036 (3)0.027 (2)0.006 (2)−0.0049 (18)−0.0074 (18)
O70.0370 (18)0.0379 (19)0.0205 (15)0.0059 (14)−0.0067 (12)−0.0043 (12)
O40.0414 (19)0.0353 (18)0.0218 (15)−0.0024 (15)−0.0011 (13)−0.0026 (12)
O100.0360 (18)0.0360 (19)0.0217 (15)−0.0011 (14)0.0076 (12)−0.0036 (12)
O10.041 (2)0.0336 (18)0.0199 (15)0.0036 (15)−0.0018 (13)−0.0023 (12)
O90.0288 (17)0.0393 (19)0.0248 (15)−0.0096 (14)0.0014 (12)−0.0033 (13)
C20.021 (2)0.034 (3)0.023 (2)−0.0046 (19)−0.0009 (16)−0.0015 (17)
O80.0279 (16)0.0377 (19)0.0260 (15)0.0076 (14)−0.0030 (12)−0.0009 (13)
O20.0337 (18)0.0352 (19)0.0258 (15)0.0051 (14)−0.0005 (12)0.0009 (13)
N10.0240 (19)0.037 (2)0.0232 (18)0.0005 (17)0.0012 (14)−0.0012 (15)
O50.0374 (19)0.039 (2)0.0242 (16)−0.0067 (15)−0.0007 (12)0.0009 (13)
N20.029 (2)0.035 (2)0.0262 (19)−0.0013 (17)−0.0017 (15)0.0020 (15)
C30.029 (3)0.038 (3)0.024 (2)−0.001 (2)0.0017 (17)−0.0009 (18)
O30.044 (2)0.046 (2)0.0234 (15)−0.0087 (17)0.0108 (13)−0.0042 (13)
C40.021 (2)0.039 (3)0.023 (2)0.005 (2)−0.0016 (16)−0.0005 (18)
O60.055 (2)0.052 (2)0.0273 (17)0.0177 (18)−0.0158 (15)−0.0076 (15)
C50.028 (2)0.036 (3)0.028 (2)0.001 (2)−0.0014 (17)−0.0052 (18)
C60.026 (2)0.029 (2)0.0177 (19)−0.0035 (18)0.0016 (15)0.0002 (15)
C70.024 (2)0.032 (3)0.030 (2)−0.0041 (19)0.0001 (18)−0.0045 (17)
C80.025 (2)0.032 (3)0.026 (2)−0.0004 (19)0.0006 (17)−0.0038 (17)
C90.025 (2)0.029 (2)0.020 (2)−0.0009 (19)−0.0022 (15)0.0003 (16)
C100.026 (2)0.030 (2)0.023 (2)0.0022 (18)−0.0001 (16)−0.0024 (16)
C110.026 (2)0.033 (3)0.025 (2)0.0010 (19)0.0031 (16)−0.0037 (17)
C120.027 (2)0.030 (3)0.025 (2)−0.0011 (19)0.0061 (16)−0.0040 (17)
C130.026 (2)0.031 (3)0.024 (2)0.0010 (19)−0.0047 (16)−0.0030 (17)
C140.032 (2)0.029 (2)0.021 (2)0.000 (2)0.0030 (17)−0.0027 (17)
C150.037 (3)0.033 (3)0.024 (2)0.002 (2)−0.0084 (18)−0.0072 (18)
C160.034 (3)0.027 (3)0.029 (2)0.004 (2)0.0043 (18)−0.0050 (17)
C170.035 (3)0.047 (3)0.027 (2)0.000 (2)−0.0001 (19)0.000 (2)
C180.039 (3)0.033 (3)0.037 (3)−0.001 (2)−0.006 (2)0.008 (2)
C190.039 (3)0.034 (3)0.042 (3)0.005 (2)−0.003 (2)−0.001 (2)
C200.043 (3)0.036 (3)0.040 (3)0.006 (2)0.004 (2)0.000 (2)
C210.050 (3)0.032 (3)0.046 (3)−0.012 (2)0.012 (2)0.001 (2)
C220.037 (3)0.048 (3)0.028 (2)−0.008 (2)0.0046 (19)−0.010 (2)
C230.041 (3)0.041 (3)0.039 (3)−0.001 (2)0.000 (2)0.002 (2)
C240.051 (4)0.031 (3)0.072 (4)−0.005 (3)0.008 (3)0.006 (3)
C250.059 (4)0.037 (3)0.049 (3)−0.011 (3)0.012 (3)0.004 (2)
C260.072 (5)0.057 (4)0.044 (3)0.021 (3)−0.015 (3)−0.001 (3)
C270.070 (4)0.038 (3)0.064 (4)0.007 (3)0.004 (3)0.001 (3)
C280.052 (3)0.038 (3)0.041 (3)−0.013 (3)0.011 (2)−0.007 (2)
C290.040 (3)0.049 (3)0.035 (3)0.009 (2)−0.003 (2)−0.010 (2)
C300.054 (4)0.039 (4)0.097 (5)0.003 (3)−0.031 (3)0.006 (3)
C310.080 (5)0.045 (4)0.044 (3)0.006 (3)−0.008 (3)0.010 (3)
C320.051 (4)0.043 (4)0.145 (7)0.005 (3)0.050 (4)0.010 (4)
Geometric parameters (Å, °) top
C1—O61.424 (5)C12—H12B0.9700
C1—C151.516 (7)C13—H13A0.9700
C1—C41.535 (6)C13—H13B0.9700
C1—H10.9800C14—C181.381 (6)
O7—C61.279 (5)C14—C171.392 (6)
O4—C41.315 (5)C15—C231.375 (7)
O4—H40.8200C15—C191.410 (7)
O10—C91.292 (5)C16—C201.554 (7)
O1—C21.317 (5)C16—H16A0.9700
O1—H1A0.8200C16—H16B0.9700
O9—C91.255 (5)C17—C221.380 (7)
C2—O21.210 (5)C17—H170.9300
C2—C111.528 (6)C18—C251.393 (7)
O8—C61.240 (5)C18—H180.9300
N1—C51.486 (6)C19—C291.366 (7)
N1—H1B0.8900C19—H190.9300
N1—H1C0.8900C20—C271.515 (8)
N1—H1D0.8900C20—C301.516 (8)
O5—C41.207 (5)C20—H200.9800
N2—C31.488 (6)C21—C241.515 (7)
N2—H2A0.8900C21—C321.522 (8)
N2—H2B0.8900C21—H210.9800
N2—H2C0.8900C22—C281.365 (7)
C3—C101.540 (6)C22—H220.9300
C3—H3A0.9700C23—C311.384 (8)
C3—H3B0.9700C23—H230.9300
O3—C111.426 (5)C24—H24A0.9600
O3—H30.8200C24—H24B0.9600
O6—H60.8200C24—H24C0.9600
C5—C81.526 (6)C25—C281.377 (8)
C5—H5A0.9700C25—H250.9300
C5—H5B0.9700C26—C311.368 (9)
C6—C131.508 (6)C26—C291.402 (8)
C7—C101.530 (6)C26—H260.9300
C7—C211.532 (6)C27—H27A0.9600
C7—H7A0.9700C27—H27B0.9600
C7—H7B0.9700C27—H27C0.9600
C8—C161.541 (6)C28—H280.9300
C8—C121.552 (6)C29—H290.9300
C8—H80.9800C30—H30A0.9600
C9—C121.506 (6)C30—H30B0.9600
C10—C131.536 (6)C30—H30C0.9600
C10—H100.9800C31—H310.9300
C11—C141.525 (6)C32—H32A0.9600
C11—H110.9800C32—H32B0.9600
C12—H12A0.9700C32—H32C0.9600
O6—C1—C15107.3 (3)C10—C13—H13B108.1
O6—C1—C4111.3 (4)H13A—C13—H13B107.3
C15—C1—C4110.2 (4)C18—C14—C17119.1 (4)
O6—C1—H1109.3C18—C14—C11121.2 (4)
C15—C1—H1109.3C17—C14—C11119.7 (4)
C4—C1—H1109.3C23—C15—C19118.3 (5)
C4—O4—H4109.5C23—C15—C1121.9 (4)
C2—O1—H1A109.5C19—C15—C1119.8 (4)
O2—C2—O1124.0 (4)C8—C16—C20115.7 (4)
O2—C2—C11124.4 (4)C8—C16—H16A108.3
O1—C2—C11111.6 (4)C20—C16—H16A108.3
C5—N1—H1B109.5C8—C16—H16B108.3
C5—N1—H1C109.5C20—C16—H16B108.3
H1B—N1—H1C109.5H16A—C16—H16B107.4
C5—N1—H1D109.5C22—C17—C14120.1 (5)
H1B—N1—H1D109.5C22—C17—H17119.9
H1C—N1—H1D109.5C14—C17—H17119.9
C3—N2—H2A109.5C14—C18—C25119.0 (5)
C3—N2—H2B109.5C14—C18—H18120.5
H2A—N2—H2B109.5C25—C18—H18120.5
C3—N2—H2C109.5C29—C19—C15120.4 (5)
H2A—N2—H2C109.5C29—C19—H19119.8
H2B—N2—H2C109.5C15—C19—H19119.8
N2—C3—C10112.0 (3)C27—C20—C30110.6 (5)
N2—C3—H3A109.2C27—C20—C16109.6 (4)
C10—C3—H3A109.2C30—C20—C16112.8 (4)
N2—C3—H3B109.2C27—C20—H20107.9
C10—C3—H3B109.2C30—C20—H20107.9
H3A—C3—H3B107.9C16—C20—H20107.9
C11—O3—H3109.5C24—C21—C32110.3 (5)
O5—C4—O4124.6 (4)C24—C21—C7110.0 (4)
O5—C4—C1124.2 (4)C32—C21—C7113.4 (5)
O4—C4—C1111.2 (4)C24—C21—H21107.7
C1—O6—H6109.5C32—C21—H21107.7
N1—C5—C8112.4 (3)C7—C21—H21107.7
N1—C5—H5A109.1C28—C22—C17121.7 (5)
C8—C5—H5A109.1C28—C22—H22119.1
N1—C5—H5B109.1C17—C22—H22119.1
C8—C5—H5B109.1C15—C23—C31121.8 (5)
H5A—C5—H5B107.9C15—C23—H23119.1
O8—C6—O7123.8 (4)C31—C23—H23119.1
O8—C6—C13120.4 (4)C21—C24—H24A109.5
O7—C6—C13115.8 (4)C21—C24—H24B109.5
C10—C7—C21115.5 (4)H24A—C24—H24B109.5
C10—C7—H7A108.4C21—C24—H24C109.5
C21—C7—H7A108.4H24A—C24—H24C109.5
C10—C7—H7B108.4H24B—C24—H24C109.5
C21—C7—H7B108.4C28—C25—C18122.1 (5)
H7A—C7—H7B107.5C28—C25—H25118.9
C5—C8—C16108.0 (3)C18—C25—H25118.9
C5—C8—C12112.2 (4)C31—C26—C29120.5 (6)
C16—C8—C12111.5 (4)C31—C26—H26119.7
C5—C8—H8108.3C29—C26—H26119.7
C16—C8—H8108.3C20—C27—H27A109.5
C12—C8—H8108.3C20—C27—H27B109.5
O9—C9—O10124.2 (4)H27A—C27—H27B109.5
O9—C9—C12120.3 (4)C20—C27—H27C109.5
O10—C9—C12115.5 (4)H27A—C27—H27C109.5
C7—C10—C13111.8 (4)H27B—C27—H27C109.5
C7—C10—C3108.9 (3)C22—C28—C25117.9 (5)
C13—C10—C3112.1 (4)C22—C28—H28121.1
C7—C10—H10108.0C25—C28—H28121.1
C13—C10—H10108.0C19—C29—C26119.7 (5)
C3—C10—H10108.0C19—C29—H29120.1
O3—C11—C14107.2 (3)C26—C29—H29120.1
O3—C11—C2112.1 (4)C20—C30—H30A109.5
C14—C11—C2109.8 (3)C20—C30—H30B109.5
O3—C11—H11109.2H30A—C30—H30B109.5
C14—C11—H11109.2C20—C30—H30C109.5
C2—C11—H11109.2H30A—C30—H30C109.5
C9—C12—C8115.9 (4)H30B—C30—H30C109.5
C9—C12—H12A108.3C26—C31—C23119.1 (5)
C8—C12—H12A108.3C26—C31—H31120.4
C9—C12—H12B108.3C23—C31—H31120.4
C8—C12—H12B108.3C21—C32—H32A109.5
H12A—C12—H12B107.4C21—C32—H32B109.5
C6—C13—C10116.9 (4)H32A—C32—H32B109.5
C6—C13—H13A108.1C21—C32—H32C109.5
C10—C13—H13A108.1H32A—C32—H32C109.5
C6—C13—H13B108.1H32B—C32—H32C109.5
O6—C1—C4—O5−7.7 (6)O6—C1—C15—C23−129.1 (5)
C15—C1—C4—O5111.3 (5)C4—C1—C15—C23109.5 (5)
O6—C1—C4—O4173.5 (4)O6—C1—C15—C1948.5 (5)
C15—C1—C4—O4−67.5 (5)C4—C1—C15—C19−72.9 (5)
N1—C5—C8—C16180.0 (4)C5—C8—C16—C20−168.5 (4)
N1—C5—C8—C12−56.7 (5)C12—C8—C16—C2067.7 (5)
C21—C7—C10—C1367.5 (5)C18—C14—C17—C221.9 (6)
C21—C7—C10—C3−168.1 (4)C11—C14—C17—C22−176.9 (4)
N2—C3—C10—C7179.5 (4)C17—C14—C18—C25−0.5 (7)
N2—C3—C10—C13−56.2 (5)C11—C14—C18—C25178.2 (4)
O2—C2—C11—O3−10.0 (6)C23—C15—C19—C291.9 (7)
O1—C2—C11—O3170.5 (4)C1—C15—C19—C29−175.9 (4)
O2—C2—C11—C14109.0 (5)C8—C16—C20—C27179.8 (4)
O1—C2—C11—C14−70.4 (4)C8—C16—C20—C3056.2 (6)
O9—C9—C12—C8−4.7 (6)C10—C7—C21—C24179.5 (5)
O10—C9—C12—C8173.5 (4)C10—C7—C21—C3255.6 (6)
C5—C8—C12—C989.1 (5)C14—C17—C22—C28−1.0 (7)
C16—C8—C12—C9−149.6 (4)C19—C15—C23—C31−1.6 (7)
O8—C6—C13—C10−4.2 (6)C1—C15—C23—C31176.1 (5)
O7—C6—C13—C10173.8 (4)C14—C18—C25—C28−1.8 (8)
C7—C10—C13—C6−148.1 (4)C17—C22—C28—C25−1.2 (7)
C3—C10—C13—C689.3 (5)C18—C25—C28—C222.6 (8)
O3—C11—C14—C18−131.2 (4)C15—C19—C29—C26−1.3 (7)
C2—C11—C14—C18106.8 (5)C31—C26—C29—C190.5 (8)
O3—C11—C14—C1747.6 (5)C29—C26—C31—C23−0.2 (9)
C2—C11—C14—C17−74.5 (5)C15—C23—C31—C260.8 (8)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O4—H4···O100.821.692.501 (4)173
O1—H1A···O7i0.821.682.493 (4)171
N1—H1B···O80.891.922.808 (5)172
N1—H1C···O7ii0.892.233.052 (5)154
N1—H1D···O5iii0.891.932.812 (5)172
N2—H2A···O9iv0.891.902.771 (5)167
N2—H2B···O100.892.193.048 (5)163
N2—H2C···O20.891.942.804 (4)163
O3—H3···O100.821.922.708 (4)160
O6—H6···O7v0.821.882.689 (4)167
Symmetry codes: (i) x, y, z−1; (ii) x−1, y, z; (iii) x, y, z+1; (iv) x+1, y, z; (v) x−1, y, z−1.
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O4—H4···O100.821.692.501 (4)173
O1—H1A···O7i0.821.682.493 (4)171
N1—H1B···O80.891.922.808 (5)172
N1—H1C···O7ii0.892.233.052 (5)154
N1—H1D···O5iii0.891.932.812 (5)172
N2—H2A···O9iv0.891.902.771 (5)167
N2—H2B···O100.892.193.048 (5)163
N2—H2C···O20.891.942.804 (4)163
O3—H3···O100.821.922.708 (4)160
O6—H6···O7v0.821.882.689 (4)167
Symmetry codes: (i) x, y, z−1; (ii) x−1, y, z; (iii) x, y, z+1; (iv) x+1, y, z; (v) x−1, y, z−1.
references
References top

Bruker (2003). SMART (Version 5.630 for WNT/2000), SAINT-Plus (Version 6.45) and SHELXTL (Version 6.14). Bruker AXS Inc., Madison, Wisconsin, USA.

Flack, H. D. (1983). Acta Cryst. A39, 876–881.

Hoekstra, M. S., Sobieray, D. M., Schwindt, M. A., Mulhern, T. A., Grote, T. M., Huckabee, B. K., Hendrickson, V. S., Franklin, L. C., Granger, E. J. & Karrick, G. L. (1997). Org. Process Res. Dev. 1, 26–38.

Mulhern, T. A. (1996). A Practical Synthesis of (S)-Isobutyl GABA, an Anticonvulsant. The Gordon Conference, Location?, 16 July 1996. Abstract number?

Pope, W. J. & Peachey, J. (1899). J. Chem. Soc. 75, 1066–1093.

Sheldrick, G. M. (1996). XP. University of Göttingen, Germany. [Please check added reference]

Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Göttingen, Germany.

Sheldrick, G. M. (2003). SADABS. Version 2.10. University of Göttingen, Germany. [Please check year - 2003 here, but originally cited as 2002.]

Siemens (1991). XSCANS. Version 5.0. Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA.