tert-Butyl 4-(3,4-dichloro­anilino)piperidine-1-carboxyl­ate

Mehr-un-Nisa; Munawar, M.A.; Hall, G.B.; Roberts, S.A.; Hruby, V.J.

doi:10.1107/S1600536812051896

organic compounds

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ISSN: 2056-9890

Volume 69| Part 2| February 2013| Page o205

doi:10.1107/S1600536812051896

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tert-Butyl 4-(3,4-dichloroanilino)piperidine-1-carboxylate

Mehr-un-Nisa,^a Munawar Ali Munawar,^a Gabriel B. Hall,^b Sue A. Roberts ^b ^* and Victor J. Hruby ^b

^aInstitute of Chemistry, University of The Punjab, Qaid-i-Azam Campus, Lahore 54590, Pakistan, and ^bDepartment of Chemistry and Biochemistry, 1306 E University Boulevard, The University of Arizona, Tucson, AZ 85721, USA
^*Correspondence e-mail: suer@email.arizona.edu

(Received 20 December 2012; accepted 26 December 2012; online 9 January 2013)

In the title compound, C₁₆H₂₂Cl₂N₂O₂, the substituted piperidine ring adopts a chair conformation with both substituents in equatorial positions. In the crystal, N—H⋯O and C—H⋯O hydrogen bonds connect molecules into ribbons along the a-axis direction.

Related literature

For the biological activity of piperazine derivatives, see: Hamed et al. (2012 ); Joergen et al. (1997 ); Peter et al. (2009 ). For the synthesis of the title compound, see: Vardanyan et al. (2009 ).

Experimental

Crystal data

C₁₆H₂₂Cl₂N₂O₂
M_r = 345.25
Orthorhombic, P 2₁ 2₁ 2₁
a = 9.7825 (6) Å
b = 10.6075 (6) Å
c = 16.8215 (10) Å
V = 1745.53 (18) Å³
Z = 4
Mo Kα radiation
μ = 0.38 mm⁻¹
T = 100 K
0.40 × 0.40 × 0.30 mm

Data collection

Bruker Kappa APEXII DUO CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ) T_min = 0.662, T_max = 0.749
34136 measured reflections
13197 independent reflections
11079 reflections with I > 2σ(I)
R_int = 0.024

Refinement

R[F² > 2σ(F²)] = 0.034
wR(F²) = 0.079
S = 1.00
13197 reflections
202 parameters
H-atom parameters constrained
Δρ_max = 0.44 e Å⁻³
Δρ_min = −0.19 e Å⁻³
Absolute structure: Flack (1983 ), 6110 Friedel pairs
Flack parameter: −0.01 (2)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O2ⁱ	0.88	2.12	2.9740 (8)	163
C3—H3⋯O2ⁱ	0.95	2.58	3.3486 (9)	138
Symmetry code: (i) $[x+{\script{1\over 2}}, -y+{\script{3\over 2}}, -z+1]$ .

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009 ); software used to prepare material for publication: publCIF (Westrip, 2010 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536812051896/zl2529sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812051896/zl2529Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536812051896/zl2529Isup3.cml

checkCIF report

Comment top

Piperazine derivatives have been shown to inhibit re-uptake of the monoamines dopamine, noradrenaline and serotonin in synaptosomes (Joergen et al., 1997), and their use for the treatment of protozoal infections, particularly malaria, has also been reported (Hamed et al., 2012). Selective serotonin reuptake inhibitors (SSRI) provide efficacy in the treatment of numerous CNS disorders, including depression and panic disorders, and are usually observed to be effective, well tolerated and simply administered (Peter et al., 2009)). During our search to find new synthetic novel multivalent ligands for the treatment of pain and depression, the title compound was synthesized as an intermediate. Compounds prepared from this intermediate are now under study for possible opioid and SSRIs activities.

The piperidine ring is in a chair conformation with both substituents in equatorial positions. An intermolecular hydrogen bond is present between N1—H1 and O2 with a donor-hydrogen-acceptor angle of 163.40° and a donor-aceptor distance of 2.9740 (8) Å. Hydrogen bonds connect molecules into ribbons extending in the crystallographic a direction. The hydrogen bonding graph set is C1,1(8)a.

Related literature top

For the biological activity of piperazine derivatives, see: Hamed et al. (2012); Joergen et al. (1997); Peter et al. (2009). For the synthesis of the title compound, see: Vardanyan et al. (2009).

Experimental top

tert-Butyl 4-((3,4-dichlorophenyl)amino)piperidine-1-carboxylate (1) was synthesized by modification of a reported method (Vardanyan et al., 2009) by refluxing N-Boc-4-piperidone (5.0 g, 25.1 mmol) and 3,4-dichloroaniline (4.07 g, 25.1 mmol) in toluene (100 ml) with a catalytic amount of p-toluene sulphonic acid using a Dean and Stark apparatus for 4–5 h. The reaction was left to cool overnight. Toluene was evaporated under reduced pressure. The crude product was dissolved in diethyl ether, passed through a bed of neutral alumina, and the ether evaporated under reduced pressure. The residue was dissolved in CH₃OH (50 ml) and NaBH₄ (1.05 g, 27.6 mmol) was added slowly at room temperature. The reaction mixture was left to stir overnight. The reaction was quenched with aqueous NaHCO₃ (5 ml). The solvent was removed under reduced pressure and the residue was dissolved in diethyl ether, dried over anhydrous MgSO₄, filtered and evaporated under reduced pressure. The residue was recrystallized from CH₃OH to obtain (1) as a white crystalline solid. Crystals appropriate for X-ray diffraction were grown from methanol by slow evaporation at room temperature. 8.22 g (95%) yield; m.p. 155–157 °C; MS (ESI): m/z: [M+H]⁺: 345; HRMS: Calcd for C₁₆H₂₃Cl₂N₂O₂: 345.113; found: 345.1131.

Computing details top

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: publCIF (Westrip, 2010).

Figures top

	Fig. 1. The molecular structure of the title compound. Anisotropically refined atoms are shown as 50% probability ellipsoids.
	Fig. 2. Hydrogen bonding interactions, shown as dashed lines. The molecules are connected into a chain running along the a direction in the crystal.

tert-Butyl 4-(3,4-dichloroanilino)piperidine-1-carboxylate top

Crystal data top

C₁₆H₂₂Cl₂N₂O₂	D_x = 1.302 Mg m⁻³
M_r = 345.25	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 9939 reflections
a = 9.7825 (6) Å	θ = 2.8–40.0°
b = 10.6075 (6) Å	µ = 0.38 mm⁻¹
c = 16.8215 (10) Å	T = 100 K
V = 1745.53 (18) Å³	Rod, clear colourless
Z = 4	0.40 × 0.40 × 0.30 mm
F(000) = 728

Data collection top

Bruker Kappa APEXII DUO CCD diffractometer	13197 independent reflections
Radiation source: fine-focus sealed tube	11079 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.024
Detector resolution: 8.3333 pixels mm^-1	θ_max = 43.7°, θ_min = 2.3°
ϕ and ω scans	h = −19→17
Absorption correction: multi-scan (SADABS; Bruker, 2009)	k = −20→15
T_min = 0.662, T_max = 0.749	l = −32→22
34136 measured reflections

Refinement top

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)] = 0.034	H-atom parameters constrained
wR(F²) = 0.079	w = 1/[σ²(F_o²) + (0.0361P)² + 0.1129P] where P = (F_o² + 2F_c²)/3
S = 1.00	(Δ/σ)_max = 0.002
13197 reflections	Δρ_max = 0.44 e Å⁻³
202 parameters	Δρ_min = −0.19 e Å⁻³
0 restraints	Absolute structure: Flack (1983), ???? Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.01 (2)

Crystal data top

C₁₆H₂₂Cl₂N₂O₂	V = 1745.53 (18) Å³
M_r = 345.25	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 9.7825 (6) Å	µ = 0.38 mm⁻¹
b = 10.6075 (6) Å	T = 100 K
c = 16.8215 (10) Å	0.40 × 0.40 × 0.30 mm

Data collection top

Bruker Kappa APEXII DUO CCD diffractometer	13197 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2009)	11079 reflections with I > 2σ(I)
T_min = 0.662, T_max = 0.749	R_int = 0.024
34136 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.034	H-atom parameters constrained
wR(F²) = 0.079	Δρ_max = 0.44 e Å⁻³
S = 1.00	Δρ_min = −0.19 e Å⁻³
13197 reflections	Absolute structure: Flack (1983), ???? Friedel pairs
202 parameters	Absolute structure parameter: −0.01 (2)
0 restraints

Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
Cl1	−0.08164 (2)	0.97197 (2)	0.972015 (11)	0.02294 (4)
Cl2	0.13863 (19)	0.75577 (18)	0.941766 (10)	0.01982 (3)
O1	0.10534 (5)	0.83348 (5)	0.29230 (3)	0.01589 (9)
O2	−0.11737 (5)	0.79311 (6)	0.32343 (3)	0.01988 (10)
C14	0.06777 (12)	0.63102 (8)	0.22473 (6)	0.03006 (19)
H14A	0.1276	0.595	0.2655	0.045*
H14B	0.0822	0.5867	0.1743	0.045*
H14C	−0.0278	0.6217	0.2412	0.045*
C3	0.13364 (7)	0.82954 (6)	0.78917 (4)	0.01425 (10)
H3	0.2006	0.7658	0.7815	0.017*
C13	0.10078 (8)	0.77016 (7)	0.21416 (4)	0.01681 (11)
C12	−0.00406 (7)	0.83543 (6)	0.34047 (4)	0.01344 (10)
N2	0.02566 (6)	0.89021 (6)	0.41112 (4)	0.01450 (9)
C10	0.15552 (7)	0.95171 (7)	0.43015 (4)	0.01648 (11)
H10A	0.1433	1.0444	0.4296	0.02*
H10B	0.2247	0.9295	0.3895	0.02*
C11	0.20526 (7)	0.90986 (8)	0.51199 (4)	0.01733 (12)
H11A	0.2881	0.9585	0.5263	0.021*
H11B	0.2306	0.8196	0.5099	0.021*
C7	0.09632 (7)	0.92909 (7)	0.57613 (4)	0.01480 (10)
H7	0.0784	1.0215	0.5816	0.018*
N1	0.14933 (7)	0.88223 (7)	0.65131 (4)	0.01898 (11)
H1	0.2255	0.8381	0.6502	0.023*
C4	0.08893 (7)	0.90197 (6)	0.72395 (4)	0.01433 (10)
C5	−0.01262 (8)	0.99380 (7)	0.73731 (4)	0.01686 (12)
H5	−0.0468	1.0417	0.6939	0.02*
C6	−0.06310 (7)	1.01490 (7)	0.81332 (4)	0.01730 (11)
H6	−0.1303	1.0783	0.8215	0.021*
C1	−0.01660 (7)	0.94440 (7)	0.87772 (4)	0.01538 (11)
C2	0.08092 (7)	0.85036 (6)	0.86435 (4)	0.01397 (10)
C9	−0.08241 (7)	0.91113 (7)	0.46944 (4)	0.01573 (10)
H9A	−0.1662	0.8659	0.4528	0.019*
H9B	−0.1039	1.0022	0.4724	0.019*
C8	−0.03699 (7)	0.86400 (7)	0.55099 (4)	0.01653 (11)
H8A	−0.0228	0.7716	0.549	0.02*
H8B	−0.1092	0.8818	0.5906	0.02*
C16	0.24662 (8)	0.78782 (8)	0.18424 (5)	0.02256 (14)
H16A	0.2688	0.8779	0.1832	0.034*
H16B	0.2547	0.753	0.1305	0.034*
H16C	0.3101	0.7439	0.2198	0.034*
C15	0.00084 (9)	0.83714 (10)	0.15914 (5)	0.02569 (16)
H15A	−0.0908	0.8352	0.1826	0.039*
H15B	−0.0007	0.7944	0.1075	0.039*
H15C	0.0297	0.9249	0.1519	0.039*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.01965 (7)	0.03505 (10)	0.01412 (7)	0.00661 (7)	0.00311 (6)	0.00055 (6)
Cl2	0.02267 (7)	0.02154 (7)	0.01526 (6)	0.00232 (6)	−0.00074 (6)	0.00598 (6)
O1	0.0154 (2)	0.0189 (2)	0.01340 (19)	−0.00364 (16)	0.00210 (15)	−0.00379 (17)
O2	0.0162 (2)	0.0272 (3)	0.0163 (2)	−0.00867 (19)	−0.00053 (17)	−0.00255 (19)
C14	0.0419 (5)	0.0163 (3)	0.0320 (4)	−0.0073 (3)	0.0078 (4)	−0.0062 (3)
C3	0.0142 (2)	0.0149 (2)	0.0137 (2)	0.0010 (2)	−0.0004 (2)	0.0009 (2)
C13	0.0203 (3)	0.0166 (3)	0.0135 (2)	−0.0034 (2)	0.0022 (2)	−0.0035 (2)
C12	0.0144 (2)	0.0139 (2)	0.0120 (2)	−0.0024 (2)	−0.00017 (19)	0.00076 (19)
N2	0.0122 (2)	0.0189 (2)	0.0124 (2)	−0.00349 (18)	0.00084 (17)	−0.00202 (18)
C10	0.0145 (2)	0.0219 (3)	0.0131 (2)	−0.0061 (2)	−0.0004 (2)	0.0001 (2)
C11	0.0132 (2)	0.0253 (3)	0.0135 (3)	0.0000 (2)	−0.0002 (2)	−0.0005 (2)
C7	0.0151 (2)	0.0174 (3)	0.0119 (2)	0.0014 (2)	−0.00057 (19)	0.0005 (2)
N1	0.0201 (3)	0.0252 (3)	0.0116 (2)	0.0098 (2)	0.0005 (2)	0.0014 (2)
C4	0.0145 (2)	0.0160 (2)	0.0124 (2)	0.0019 (2)	0.0001 (2)	0.00067 (19)
C5	0.0173 (3)	0.0190 (3)	0.0142 (3)	0.0052 (2)	0.0003 (2)	0.0022 (2)
C6	0.0166 (3)	0.0199 (3)	0.0155 (3)	0.0044 (2)	0.0011 (2)	0.0010 (2)
C1	0.0140 (2)	0.0188 (3)	0.0133 (2)	0.0005 (2)	0.0013 (2)	0.0004 (2)
C2	0.0135 (2)	0.0150 (2)	0.0134 (2)	−0.0005 (2)	−0.0013 (2)	0.00250 (19)
C9	0.0132 (2)	0.0197 (3)	0.0143 (2)	−0.0003 (2)	0.0008 (2)	−0.0017 (2)
C8	0.0159 (3)	0.0197 (3)	0.0140 (3)	−0.0014 (2)	0.0024 (2)	0.0007 (2)
C16	0.0219 (3)	0.0250 (3)	0.0208 (3)	−0.0014 (3)	0.0062 (3)	−0.0042 (3)
C15	0.0246 (3)	0.0378 (4)	0.0147 (3)	0.0000 (3)	−0.0006 (3)	0.0007 (3)

Geometric parameters (Å, º) top

Cl1—C1	1.7338 (7)	C7—N1	1.4544 (9)
Cl2—C2	1.7382 (7)	C7—C8	1.5350 (10)
O1—C12	1.3425 (8)	C7—H7	1.0
O1—C13	1.4767 (8)	N1—C4	1.3734 (9)
O2—C12	1.2298 (8)	N1—H1	0.88
C14—C13	1.5213 (11)	C4—C5	1.4093 (10)
C14—H14A	0.98	C5—C6	1.3888 (10)
C14—H14B	0.98	C5—H5	0.95
C14—H14C	0.98	C6—C1	1.3928 (10)
C3—C2	1.3835 (10)	C6—H6	0.95
C3—C4	1.4090 (9)	C1—C2	1.3984 (10)
C3—H3	0.95	C9—C8	1.5261 (10)
C13—C15	1.5223 (12)	C9—H9A	0.99
C13—C16	1.5244 (11)	C9—H9B	0.99
C12—N2	1.3545 (9)	C8—H8A	0.99
N2—C9	1.4592 (9)	C8—H8B	0.99
N2—C10	1.4635 (9)	C16—H16A	0.98
C10—C11	1.5260 (10)	C16—H16B	0.98
C10—H10A	0.99	C16—H16C	0.98
C10—H10B	0.99	C15—H15A	0.98
C11—C7	1.5302 (10)	C15—H15B	0.98
C11—H11A	0.99	C15—H15C	0.98
C11—H11B	0.99

C12—O1—C13	121.34 (5)	C4—N1—H1	117.7
C13—C14—H14A	109.5	C7—N1—H1	117.7
C13—C14—H14B	109.5	N1—C4—C3	118.43 (6)
H14A—C14—H14B	109.5	N1—C4—C5	123.40 (6)
C13—C14—H14C	109.5	C3—C4—C5	118.14 (6)
H14A—C14—H14C	109.5	C6—C5—C4	120.58 (6)
H14B—C14—H14C	109.5	C6—C5—H5	119.7
C2—C3—C4	120.59 (6)	C4—C5—H5	119.7
C2—C3—H3	119.7	C5—C6—C1	120.90 (7)
C4—C3—H3	119.7	C5—C6—H6	119.6
O1—C13—C15	110.38 (6)	C1—C6—H6	119.6
O1—C13—C16	102.11 (6)	C6—C1—C2	118.73 (6)
C15—C13—C16	110.06 (7)	C6—C1—Cl1	120.08 (5)
O1—C13—C14	110.10 (6)	C2—C1—Cl1	121.19 (5)
C15—C13—C14	112.80 (7)	C3—C2—C1	121.01 (6)
C16—C13—C14	110.89 (7)	C3—C2—Cl2	118.14 (5)
O2—C12—O1	124.91 (6)	C1—C2—Cl2	120.85 (5)
O2—C12—N2	123.67 (6)	N2—C9—C8	110.10 (6)
O1—C12—N2	111.42 (6)	N2—C9—H9A	109.6
C12—N2—C9	119.98 (6)	C8—C9—H9A	109.6
C12—N2—C10	124.71 (6)	N2—C9—H9B	109.6
C9—N2—C10	114.45 (6)	C8—C9—H9B	109.6
N2—C10—C11	110.14 (6)	H9A—C9—H9B	108.2
N2—C10—H10A	109.6	C9—C8—C7	110.34 (6)
C11—C10—H10A	109.6	C9—C8—H8A	109.6
N2—C10—H10B	109.6	C7—C8—H8A	109.6
C11—C10—H10B	109.6	C9—C8—H8B	109.6
H10A—C10—H10B	108.1	C7—C8—H8B	109.6
C10—C11—C7	112.04 (6)	H8A—C8—H8B	108.1
C10—C11—H11A	109.2	C13—C16—H16A	109.5
C7—C11—H11A	109.2	C13—C16—H16B	109.5
C10—C11—H11B	109.2	H16A—C16—H16B	109.5
C7—C11—H11B	109.2	C13—C16—H16C	109.5
H11A—C11—H11B	107.9	H16A—C16—H16C	109.5
N1—C7—C11	108.61 (6)	H16B—C16—H16C	109.5
N1—C7—C8	112.88 (6)	C13—C15—H15A	109.5
C11—C7—C8	109.72 (6)	C13—C15—H15B	109.5
N1—C7—H7	108.5	H15A—C15—H15B	109.5
C11—C7—H7	108.5	C13—C15—H15C	109.5
C8—C7—H7	108.5	H15A—C15—H15C	109.5
C4—N1—C7	124.62 (6)	H15B—C15—H15C	109.5

C12—O1—C13—C15	65.40 (8)	C2—C3—C4—N1	176.69 (7)
C12—O1—C13—C16	−177.61 (6)	C2—C3—C4—C5	−1.34 (10)
C12—O1—C13—C14	−59.79 (9)	N1—C4—C5—C6	−175.62 (7)
C13—O1—C12—O2	−4.42 (11)	C3—C4—C5—C6	2.31 (11)
C13—O1—C12—N2	175.50 (6)	C4—C5—C6—C1	−1.23 (12)
O2—C12—N2—C9	−5.18 (11)	C5—C6—C1—C2	−0.86 (11)
O1—C12—N2—C9	174.90 (6)	C5—C6—C1—Cl1	−179.73 (6)
O2—C12—N2—C10	−174.00 (7)	C4—C3—C2—C1	−0.72 (11)
O1—C12—N2—C10	6.08 (10)	C4—C3—C2—Cl2	178.95 (5)
C12—N2—C10—C11	−134.30 (7)	C6—C1—C2—C3	1.83 (11)
C9—N2—C10—C11	56.33 (8)	Cl1—C1—C2—C3	−179.31 (6)
N2—C10—C11—C7	−53.30 (8)	C6—C1—C2—Cl2	−177.83 (6)
C10—C11—C7—N1	177.63 (6)	Cl1—C1—C2—Cl2	1.03 (9)
C10—C11—C7—C8	53.82 (8)	C12—N2—C9—C8	131.49 (7)
C11—C7—N1—C4	169.17 (7)	C10—N2—C9—C8	−58.59 (8)
C8—C7—N1—C4	−68.92 (9)	N2—C9—C8—C7	56.87 (7)
C7—N1—C4—C3	166.47 (7)	N1—C7—C8—C9	−176.41 (6)
C7—N1—C4—C5	−15.61 (12)	C11—C7—C8—C9	−55.13 (8)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O2ⁱ	0.88	2.12	2.9740 (8)	163
C3—H3···O2ⁱ	0.95	2.58	3.3486 (9)	138

Symmetry code: (i) x+1/2, −y+3/2, −z+1.

Experimental details

Crystal data
Chemical formula	C₁₆H₂₂Cl₂N₂O₂
M_r	345.25
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	100
a, b, c (Å)	9.7825 (6), 10.6075 (6), 16.8215 (10)
V (Å³)	1745.53 (18)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.38
Crystal size (mm)	0.40 × 0.40 × 0.30

Data collection
Diffractometer	Bruker Kappa APEXII DUO CCD diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2009)
T_min, T_max	0.662, 0.749
No. of measured, independent and observed [I > 2σ(I)] reflections	34136, 13197, 11079
R_int	0.024
(sin θ/λ)_max (Å⁻¹)	0.973

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.034, 0.079, 1.00
No. of reflections	13197
No. of parameters	202
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.44, −0.19
Absolute structure	Flack (1983), ???? Friedel pairs
Absolute structure parameter	−0.01 (2)

Computer programs: APEX2 (Bruker, 2009), SAINT (Bruker, 2009), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), OLEX2 (Dolomanov et al., 2009), publCIF (Westrip, 2010).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O2ⁱ	0.88	2.12	2.9740 (8)	163.4
C3—H3···O2ⁱ	0.95	2.58	3.3486 (9)	137.8

Symmetry code: (i) x+1/2, −y+3/2, −z+1.

Acknowledgements

We gratefully acknowledge a grant from the Higher Education Commission of Pakistan under the IRSIP programme to support PhD students. The Bruker Kappa APEXII DUO was purchased with funding from NSF grant CHE-0741837. The work was supported in part by grants from the US Public Health Service and National Institutes of Health (DA06284 and DA13449).

References

Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Hamed, A., Christoph, B., Olivier, C., Bibia, H. & Romain, S. (2012). US Patent Appl. 2012316178. Google Scholar
Joergen, S.-K., Peter, M. & Frank, W. (1997). World Patent WO9730997. Google Scholar
Peter, D., Eriksen, B. L., Munro, G. & Nielsen, E. (2009). World Patent WO 2009/077585. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Vardanyan, R., Vijay, G., Nichol, G. S., Liu, L., Kumarasinghe, I., Davis, P., Vanderah, T., Porreca, F., Lai, J. & Hruby, V. J. (2009). Bioorg. Med. Chem. 14, 5044–5053. Web of Science CSD CrossRef Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar