(1S,2S,6R,7aR)-2-Benzyl-1,6-dihy­droxy­hexa­hydro­pyrrolizin-3-one

Oliveira, F.L.; Freire, K.R.L.; Aparicio, R.; Coelho, F.

doi:10.1107/S1600536812002334

organic compounds

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ISSN: 2056-9890

Volume 68| Part 3| March 2012| Page o587

doi:10.1107/S1600536812002334

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(1S,2S,6R,7aR)-2-Benzyl-1,6-dihydroxyhexahydropyrrolizin-3-one

F. L. Oliveira,^a K. R. L. Freire,^b R. Aparicio ^a ^* and F. Coelho ^b

^aLaboratory of Structural Biology and Crystallography, Institute of Chemistry, University of Campinas, CP6154, CEP 13083-970, Campinas-SP, Brazil, and ^bLaboratory of Synthesis of Natural Products and Drugs, Institute of Chemistry, University of Campinas, CP6154, CEP 13083-970, Campinas-SP, Brazil
^*Correspondence e-mail: aparicio@iqm.unicamp.br

(Received 5 December 2011; accepted 18 January 2012; online 4 February 2012)

In the title compound, C₁₄H₁₇NO₃, the dihedral angles show that the H atoms at two stereocenters are in a trans-diaxial configuration. In the crystal, the molecules are linked by O—H⋯O hydrogen bonds. The absolute configuration of the molecule has been established on the basis of refinement of the Hooft and Flack parameters.

Related literature

For a synthetic sequence for the preparation of the title compound, see: de Luna Freire et al. (2011 ). For the use of this type of compounds as LFA-1 (Lymphocyte Function-Associated Antigen-1) inhibitors, see: Baumann (2007 ). For a related structure, see: Newton et al. (2004 ).

Experimental

Crystal data

C₁₄H₁₇NO₃
M_r = 247.29
Orthorhombic, P 2₁ 2₁ 2₁
a = 6.6241 (3) Å
b = 13.6873 (6) Å
c = 13.9726 (6) Å
V = 1266.84 (10) Å³
Z = 4
Cu Kα radiation
μ = 0.74 mm⁻¹
T = 100 K
0.17 × 0.15 × 0.12 mm

Data collection

Bruker Kappa APEXII DUO diffractometer
26923 measured reflections
2295 independent reflections
2290 reflections with I > 2σ(I)
R_int = 0.026

Refinement

R[F² > 2σ(F²)] = 0.026
wR(F²) = 0.078
S = 1.15
2295 reflections
172 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.16 e Å⁻³
Absolute structure: Flack (1983 ) and Hooft et al. (2008 ) [Hooft parameter = 0.00(2), (943 Bijvoet pairs)]
Flack parameter: 0.00 (16)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3A⋯O2ⁱ	0.93 (2)	1.73 (2)	2.6395 (12)	164 (2)
O1—H1A⋯O3ⁱⁱ	0.86 (2)	1.93 (2)	2.7716 (13)	167 (19)
Symmetry codes: (i) x+1, y, z; (ii) $[-x+1, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

Data collection: APEX2 (Bruker, 2010 ); cell refinement: SAINT (Bruker, 2010); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: WinGX (Farrugia, 1999 ) and PLATON (Spek, 2009 ); software used to prepare material for publication: publCIF (Westrip, 2010) and PLATON.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536812002334/pv2494sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812002334/pv2494Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536812002334/pv2494Isup3.cml

checkCIF report

Comment top

The title compound can be used as a prototype for the development of new inhibitors of LFA-1 (lymphocyte function-associated antigen 1) with potential application as anti-inflammatory agents (Baumann, 2007). The title compound is a new asymmetric benzyl-pyrrolizidinone which has been synthesized in our laboratory and its crystal structure is presented in this article.

The title compound (Fig. 1) has four stereocenters and was prepared from a Morita-Baylis-Hillman adduct. The dihedral angles H3—C3—C4—H4 = -158° and H4—C4—C5—H5 = 163° show that H atoms 3, 4 and 5 at the two new stereocenters are in a trans-diaxial configuration. These values agree with the coupling constant values obtained for these H atoms in the ¹H NMR analysis. The crystal structure is stabilized by intermolecular hydrogen bonds (Tab. 1 & Fig. 2).

Related literature top

For a synthetic sequence for the preparation of the title compound, see: de Luna Freire et al. (2011). For the use of this type of compounds as LFA-1 (Lymphocyte Function-Associated Antigen-1) inhibitors, see: Baumann (2007). For a related structure, see: Newton et al. (2004).

Experimental top

The title compound was prepared using a synthetic sequence described in the literature (de Luna Freire et al., 2011) and purified by flash silica gel column chromatography (CH₂Cl₂:MeOH – solvent gradient: 0:100 to 97:03) to afford 0.06 g (as a white solid) in 97% yield. It was then recrystallized using the liquid-vapor saturation method, dissolved in ethanol and crystallized with a vapor pressure of a second less polar liquid (ethyl ether), in a closed camera, providing the slow formation of crystals.

Computing details top

Data collection: APEX2 (Bruker, 2010); cell refinement: SAINT (Bruker, 2010); data reduction: SAINT (Bruker, 2010); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: WinGX (Farrugia, 1999) and PLATON (Spek, 2009); software used to prepare material for publication: publCIF (Westrip, 2010) and PLATON (Spek, 2009).

Figures top

	Fig. 1. Molecular view of the title compound showing the atom-labeling scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are presented as a small spheres of arbitrary radius.
	Fig. 2. A unit cell packing diagram of the title compound showing hydrogen bonds as dashed lines.

(1S,2S,6R,7aR)-2-Benzyl-1,6- dihydroxyhexahydropyrrolizin-3-one top

Crystal data top

C₁₄H₁₇NO₃	D_x = 1.297 Mg m⁻³
M_r = 247.29	Cu Kα radiation, λ = 1.54178 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 2295 reflections
a = 6.6241 (3) Å	θ = 4.5–69.5°
b = 13.6873 (6) Å	µ = 0.74 mm⁻¹
c = 13.9726 (6) Å	T = 100 K
V = 1266.84 (10) Å³	Rectangular, colourless
Z = 4	0.17 × 0.15 × 0.12 mm
F(000) = 528

Data collection top

Bruker Kappa APEXII DUO diffractometer	2290 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.026
Graphite monochromator	θ_max = 69.5°, θ_min = 4.5°
Bruker APEX CCD area–detector scans	h = −7→7
26923 measured reflections	k = −15→16
2295 independent reflections	l = −16→16

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F² > 2σ(F²)] = 0.026	w = 1/[σ²(F_o²) + (0.0491P)² + 0.1808P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.078	(Δ/σ)_max = 0.001
S = 1.15	Δρ_max = 0.17 e Å⁻³
2295 reflections	Δρ_min = −0.16 e Å⁻³
172 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0086 (8)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983) and Hooft et al. (2008) [Hooft parameter = 0.00(2), (943 Bijvoet pairs)]'
Secondary atom site location: difference Fourier map	Absolute structure parameter: 0.00 (16)

Crystal data top

C₁₄H₁₇NO₃	V = 1266.84 (10) Å³
M_r = 247.29	Z = 4
Orthorhombic, P2₁2₁2₁	Cu Kα radiation
a = 6.6241 (3) Å	µ = 0.74 mm⁻¹
b = 13.6873 (6) Å	T = 100 K
c = 13.9726 (6) Å	0.17 × 0.15 × 0.12 mm

Data collection top

Bruker Kappa APEXII DUO diffractometer	2290 reflections with I > 2σ(I)
26923 measured reflections	R_int = 0.026
2295 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.026	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.078	Δρ_max = 0.17 e Å⁻³
S = 1.15	Δρ_min = −0.16 e Å⁻³
2295 reflections	Absolute structure: Flack (1983) and Hooft et al. (2008) [Hooft parameter = 0.00(2), (943 Bijvoet pairs)]'
172 parameters	Absolute structure parameter: 0.00 (16)
0 restraints

Special details top

Experimental. [α]_D²⁰ + 51 (c 1, MeOH); M. p. 135–136° C; IR (KBr, v_max): 3404, 3232, 2987, 2936, 2897, 2871, 1670, 1447, 1416, 1375, 1300, 1263, 1222,1175, 1121 cm-1; 1H NMR (500 MHz, CD₃OD) δ 1.55 (dddd, J = 13.4, 5.3, 4.0, 1.0 Hz, 1H, H-2 A); 2.25 (ddd, J = 13.4, 8.0, 5.4 Hz, 1H, H-2B); 2.93 (m, 2H, H-8, H-5); 3.02 (m, J = 7.5, 1.8 Hz, 1H, H-6); 3.08 (ddd, J = 12.0, 4.9, 1.3 Hz, 1H, H-14 A); 3.52 (dd, J = 12.0, 2.4 Hz, 1H, H-14B); 3.64 (m, J_H3,H4 = 7.0, J = 8.0, 5.3 Hz, 1H, H-3); 3.88 (dd,J_H4,H5 = 9.4, J_H3,H4 = 7.0 Hz, 1H, H-4); 4.41 (m, J = 5.1, 4.0, 3.0 Hz, 1H, H-1); 7.15 (m, 1H, H—Ar); 7.23 (m, 2H, H—Ar); 7.29 (m, 2H, H—Ar); ¹³C NMR (62.5 MHz, (CD₃)₂CO) δ 34.4, 38.6, 52.3, 54.0, 65.6, 72.4, 80.6, 126.5, 128.7, 130.3, 141.0, 175.6; HRMS (ESI-TOF) Calcd. for C₁₄H₁₈NO₃ [M + H]⁺ 248.1287. Found 248.1286.

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
O1	0.38278 (15)	0.66691 (6)	0.06882 (7)	0.0253 (2)
O2	−0.07013 (13)	0.91601 (7)	0.27608 (7)	0.0264 (2)
O3	0.61142 (13)	1.03167 (6)	0.28357 (7)	0.0238 (2)
N1	0.21491 (16)	0.88149 (7)	0.19167 (7)	0.0204 (3)
C1	0.3664 (2)	0.76715 (9)	0.09195 (9)	0.0217 (3)
H1	0.3789	0.8046	0.0308	0.026*
C2	0.52450 (19)	0.80862 (9)	0.16169 (9)	0.0216 (3)
H2A	0.5399	0.7667	0.2189	0.026*
H2B	0.6575	0.8168	0.1304	0.026*
C3	0.42952 (18)	0.90724 (9)	0.18696 (9)	0.0193 (3)
H3	0.4529	0.9549	0.1338	0.023*
C4	0.46008 (18)	0.95809 (9)	0.28423 (9)	0.0192 (3)
H4	0.4913	0.9084	0.3346	0.023*
C5	0.25242 (19)	1.00357 (9)	0.30318 (9)	0.0200 (3)
H5	0.2442	1.0650	0.2646	0.024*
C6	0.20002 (19)	1.03016 (9)	0.40713 (9)	0.0235 (3)
H6A	0.2759	1.0898	0.4249	0.028*
H6B	0.0544	1.0461	0.4105	0.028*
C7	0.2453 (2)	0.95143 (9)	0.48012 (9)	0.0256 (3)
C8	0.1026 (3)	0.87967 (10)	0.50128 (10)	0.0335 (3)
H8	−0.0244	0.8801	0.4697	0.040*
C9	0.1451 (3)	0.80737 (11)	0.56844 (10)	0.0428 (4)
H9	0.0466	0.7591	0.5826	0.051*
C10	0.3288 (3)	0.80545 (11)	0.61435 (10)	0.0421 (4)
H10	0.3573	0.7556	0.6597	0.050*
C11	0.10960 (19)	0.92968 (8)	0.25733 (9)	0.0210 (3)
C12	0.4306 (2)	0.94914 (10)	0.52735 (9)	0.0288 (3)
H12	0.5291	0.9976	0.5137	0.035*
C13	0.4730 (3)	0.87670 (11)	0.59435 (10)	0.0372 (4)
H13	0.5996	0.8759	0.6263	0.045*
C14	0.1616 (2)	0.79469 (9)	0.13686 (9)	0.0235 (3)
H14A	0.0595	0.8096	0.0872	0.028*
H14B	0.1101	0.7420	0.1788	0.028*
H3A	0.737 (4)	1.0009 (16)	0.2841 (14)	0.050 (5)*
H1A	0.379 (3)	0.6326 (15)	0.1204 (16)	0.043 (5)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0350 (5)	0.0173 (4)	0.0237 (4)	0.0039 (4)	0.0009 (4)	−0.0011 (3)
O2	0.0173 (4)	0.0252 (4)	0.0368 (5)	0.0013 (4)	0.0018 (4)	−0.0020 (4)
O3	0.0171 (4)	0.0209 (4)	0.0334 (5)	−0.0010 (4)	0.0019 (4)	−0.0044 (4)
N1	0.0183 (5)	0.0200 (5)	0.0229 (5)	0.0017 (4)	−0.0018 (4)	−0.0007 (4)
C1	0.0283 (7)	0.0173 (6)	0.0194 (6)	0.0033 (5)	−0.0009 (5)	0.0005 (5)
C2	0.0212 (6)	0.0210 (6)	0.0226 (6)	0.0038 (5)	0.0022 (5)	−0.0001 (5)
C3	0.0181 (6)	0.0189 (5)	0.0209 (6)	0.0020 (5)	0.0013 (4)	0.0018 (5)
C4	0.0185 (6)	0.0166 (5)	0.0226 (6)	0.0008 (4)	0.0018 (4)	−0.0003 (5)
C5	0.0188 (6)	0.0162 (5)	0.0251 (6)	0.0022 (4)	0.0024 (5)	0.0008 (5)
C6	0.0225 (6)	0.0196 (6)	0.0283 (6)	0.0001 (5)	0.0056 (5)	−0.0049 (5)
C7	0.0351 (7)	0.0200 (6)	0.0217 (6)	0.0004 (5)	0.0089 (5)	−0.0059 (5)
C8	0.0473 (9)	0.0292 (7)	0.0242 (6)	−0.0096 (6)	0.0082 (6)	−0.0073 (5)
C9	0.0763 (13)	0.0275 (7)	0.0245 (7)	−0.0166 (8)	0.0113 (8)	−0.0040 (6)
C10	0.0797 (13)	0.0242 (7)	0.0223 (7)	0.0054 (8)	0.0092 (8)	−0.0007 (5)
C11	0.0203 (6)	0.0182 (5)	0.0246 (6)	0.0039 (5)	−0.0010 (5)	0.0023 (5)
C12	0.0342 (7)	0.0259 (6)	0.0263 (6)	0.0032 (6)	0.0067 (5)	−0.0017 (5)
C13	0.0522 (10)	0.0351 (8)	0.0244 (7)	0.0117 (7)	0.0047 (7)	−0.0030 (6)
C14	0.0238 (6)	0.0227 (6)	0.0240 (6)	0.0009 (5)	−0.0033 (5)	−0.0035 (5)

Geometric parameters (Å, º) top

O1—C1	1.4138 (15)	C5—C6	1.5371 (16)
O1—H1A	0.86 (2)	C5—H5	1.0000
O2—C11	1.2333 (16)	C6—C7	1.5138 (18)
O3—C4	1.4210 (14)	C6—H6A	0.9900
O3—H3A	0.93 (2)	C6—H6B	0.9900
N1—C11	1.3279 (17)	C7—C12	1.394 (2)
N1—C14	1.4571 (16)	C7—C8	1.395 (2)
N1—C3	1.4661 (16)	C8—C9	1.392 (2)
C1—C2	1.5390 (18)	C8—H8	0.9500
C1—C14	1.5417 (18)	C9—C10	1.376 (3)
C1—H1	1.0000	C9—H9	0.9500
C2—C3	1.5306 (16)	C10—C13	1.393 (3)
C2—H2A	0.9900	C10—H10	0.9500
C2—H2B	0.9900	C12—C13	1.392 (2)
C3—C4	1.5403 (16)	C12—H12	0.9500
C3—H3	1.0000	C13—H13	0.9500
C4—C5	1.5328 (17)	C14—H14A	0.9900
C4—H4	1.0000	C14—H14B	0.9900
C5—C11	1.5258 (17)

C1—O1—H1A	109.6 (14)	C6—C5—H5	107.3
C4—O3—H3A	107.9 (14)	C7—C6—C5	115.04 (10)
C11—N1—C14	129.85 (11)	C7—C6—H6A	108.5
C11—N1—C3	114.90 (10)	C5—C6—H6A	108.5
C14—N1—C3	114.06 (10)	C7—C6—H6B	108.5
O1—C1—C2	116.78 (11)	C5—C6—H6B	108.5
O1—C1—C14	113.45 (11)	H6A—C6—H6B	107.5
C2—C1—C14	104.54 (10)	C12—C7—C8	118.72 (13)
O1—C1—H1	107.2	C12—C7—C6	120.64 (12)
C2—C1—H1	107.2	C8—C7—C6	120.64 (14)
C14—C1—H1	107.2	C9—C8—C7	120.42 (16)
C3—C2—C1	101.05 (10)	C9—C8—H8	119.8
C3—C2—H2A	111.6	C7—C8—H8	119.8
C1—C2—H2A	111.6	C10—C9—C8	120.42 (15)
C3—C2—H2B	111.6	C10—C9—H9	119.8
C1—C2—H2B	111.6	C8—C9—H9	119.8
H2A—C2—H2B	109.4	C9—C10—C13	119.97 (15)
N1—C3—C2	101.36 (10)	C9—C10—H10	120.0
N1—C3—C4	101.33 (9)	C13—C10—H10	120.0
C2—C3—C4	123.23 (10)	O2—C11—N1	125.35 (12)
N1—C3—H3	109.9	O2—C11—C5	127.58 (11)
C2—C3—H3	109.9	N1—C11—C5	107.07 (11)
C4—C3—H3	109.9	C13—C12—C7	120.81 (14)
O3—C4—C5	110.27 (9)	C13—C12—H12	119.6
O3—C4—C3	114.03 (10)	C7—C12—H12	119.6
C5—C4—C3	102.59 (10)	C12—C13—C10	119.65 (16)
O3—C4—H4	109.9	C12—C13—H13	120.2
C5—C4—H4	109.9	C10—C13—H13	120.2
C3—C4—H4	109.9	N1—C14—C1	101.53 (10)
C11—C5—C4	102.40 (9)	N1—C14—H14A	111.5
C11—C5—C6	114.43 (10)	C1—C14—H14A	111.5
C4—C5—C6	117.51 (10)	N1—C14—H14B	111.5
C11—C5—H5	107.3	C1—C14—H14B	111.5
C4—C5—H5	107.3	H14A—C14—H14B	109.3

C(11)—N(1)—C(3)—C(2)	145.23 (10)	H(1)—C(1)—C(2)—C(3)	73
C(11)—N(1)—C(3)—C(4)	17.61 (13)	H(1)—C(1)—C(2)—H(2A)	−169
C(14)—N(1)—C(3)—C(2)	−23.51 (13)	H(1)—C(1)—C(2)—H(2B)	−46
C(14)—N(1)—C(3)—C(4)	−151.12 (10)	O(1)—C(1)—C(14)—H(14A)	−86
C(3)—N(1)—C(11)—O(2)	−176.49 (12)	O(1)—C(1)—C(14)—H(14B)	36
C(3)—N(1)—C(11)—C(5)	3.73 (13)	C(2)—C(1)—C(14)—H(14A)	145
C(14)—N(1)—C(11)—O(2)	−9.9 (2)	C(2)—C(1)—C(14)—H(14B)	−92
C(14)—N(1)—C(11)—C(5)	170.29 (11)	H(1)—C(1)—C(14)—N(1)	−87
C(3)—N(1)—C(14)—C(1)	−1.76 (13)	H(1)—C(1)—C(14)—H(14A)	32
C(11)—N(1)—C(14)—C(1)	−168.41 (12)	H(1)—C(1)—C(14)—H(14B)	154
O(1)—C(1)—C(2)—C(3)	−167.02 (10)	C(1)—C(2)—C(3)—H(3)	−78
C(14)—C(1)—C(2)—C(3)	−40.78 (12)	H(2A)—C(2)—C(3)—N(1)	−81
O(1)—C(1)—C(14)—N(1)	154.80 (10)	H(2A)—C(2)—C(3)—C(4)	31
C(2)—C(1)—C(14)—N(1)	26.51 (12)	H(2A)—C(2)—C(3)—H(3)	163
C(1)—C(2)—C(3)—N(1)	38.05 (11)	H(2B)—C(2)—C(3)—N(1)	157
C(1)—C(2)—C(3)—C(4)	149.83 (11)	H(2B)—C(2)—C(3)—C(4)	−91
N(1)—C(3)—C(4)—O(3)	−149.89 (9)	H(2B)—C(2)—C(3)—H(3)	41
N(1)—C(3)—C(4)—C(5)	−30.67 (11)	N(1)—C(3)—C(4)—H(4)	86
C(2)—C(3)—C(4)—O(3)	98.31 (13)	C(2)—C(3)—C(4)—H(4)	−26
C(2)—C(3)—C(4)—C(5)	−142.47 (11)	H(3)—C(3)—C(4)—O(3)	−34
O(3)—C(4)—C(5)—C(6)	−78.74 (13)	H(3)—C(3)—C(4)—C(5)	86
O(3)—C(4)—C(5)—C(11)	154.95 (10)	H(3)—C(3)—C(4)—H(4)	−158
C(3)—C(4)—C(5)—C(6)	159.44 (10)	O(3)—C(4)—C(5)—H(5)	42
C(3)—C(4)—C(5)—C(11)	33.13 (12)	C(3)—C(4)—C(5)—H(5)	−80
C(4)—C(5)—C(6)—C(7)	−47.18 (15)	H(4)—C(4)—C(5)—C(6)	43
C(11)—C(5)—C(6)—C(7)	72.99 (14)	H(4)—C(4)—C(5)—C(11)	−84
C(4)—C(5)—C(11)—O(2)	156.61 (12)	H(4)—C(4)—C(5)—H(5)	163
C(4)—C(5)—C(11)—N(1)	−23.61 (12)	C(4)—C(5)—C(6)—H(6A)	75
C(6)—C(5)—C(11)—O(2)	28.33 (18)	C(4)—C(5)—C(6)—H(6B)	−169
C(6)—C(5)—C(11)—N(1)	−151.89 (10)	C(11)—C(5)—C(6)—H(6A)	−165
C(5)—C(6)—C(7)—C(8)	−87.85 (15)	C(11)—C(5)—C(6)—H(6B)	−49
C(5)—C(6)—C(7)—C(12)	92.02 (14)	H(5)—C(5)—C(6)—C(7)	−168
C(6)—C(7)—C(8)—C(9)	179.96 (13)	H(5)—C(5)—C(6)—H(6A)	−46
C(12)—C(7)—C(8)—C(9)	0.1 (2)	H(5)—C(5)—C(6)—H(6B)	70
C(6)—C(7)—C(12)—C(13)	−179.84 (12)	H(5)—C(5)—C(11)—O(2)	−91
C(8)—C(7)—C(12)—C(13)	0.0 (2)	H(5)—C(5)—C(11)—N(1)	89
C(7)—C(8)—C(9)—C(10)	−0.4 (2)	H(6A)—C(6)—C(7)—C(8)	150
C(8)—C(9)—C(10)—C(13)	0.6 (2)	H(6A)—C(6)—C(7)—C(12)	−30
C(9)—C(10)—C(13)—C(12)	−0.5 (2)	H(6B)—C(6)—C(7)—C(8)	34
C(7)—C(12)—C(13)—C(10)	0.2 (2)	H(6B)—C(6)—C(7)—C(12)	−146
H(1A)—O(1)—C(1)—C(2)	56.8 (14)	C(6)—C(7)—C(8)—H(8)	0
H(1A)—O(1)—C(1)—C(14)	−64.9 (14)	C(12)—C(7)—C(8)—H(8)	−180
H(1A)—O(1)—C(1)—H(1)	177	C(6)—C(7)—C(12)—H(12)	0
H(3A)—O(3)—C(4)—C(3)	−76.3 (13)	C(8)—C(7)—C(12)—H(12)	−180
H(3A)—O(3)—C(4)—C(5)	168.9 (13)	C(7)—C(8)—C(9)—H(9)	180
H(3A)—O(3)—C(4)—H(4)	48	H(8)—C(8)—C(9)—C(10)	180
C(11)—N(1)—C(3)—H(3)	−99	H(8)—C(8)—C(9)—H(9)	0
C(14)—N(1)—C(3)—H(3)	93	C(8)—C(9)—C(10)—H(10)	−179
C(3)—N(1)—C(14)—H(14A)	−121	H(9)—C(9)—C(10)—C(13)	−179
C(3)—N(1)—C(14)—H(14B)	117	H(9)—C(9)—C(10)—H(10)	1
C(11)—N(1)—C(14)—H(14A)	73	C(9)—C(10)—C(13)—H(13)	179
C(11)—N(1)—C(14)—H(14B)	−50	H(10)—C(10)—C(13)—C(12)	180
O(1)—C(1)—C(2)—H(2A)	−48	H(10)—C(10)—C(13)—H(13)	0
O(1)—C(1)—C(2)—H(2B)	74	C(7)—C(12)—C(13)—H(13)	−180
C(14)—C(1)—C(2)—H(2A)	78	H(12)—C(12)—C(13)—C(10)	−180
C(14)—C(1)—C(2)—H(2B)	−159	H(12)—C(12)—C(13)—H(13)	0

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3A···O2ⁱ	0.93 (2)	1.73 (2)	2.6395 (12)	164 (2)
O1—H1A···O3ⁱⁱ	0.86 (2)	1.93 (2)	2.7716 (13)	167 (19)

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

Experimental details

Crystal data
Chemical formula	C₁₄H₁₇NO₃
M_r	247.29
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	100
a, b, c (Å)	6.6241 (3), 13.6873 (6), 13.9726 (6)
V (Å³)	1266.84 (10)
Z	4
Radiation type	Cu Kα
µ (mm⁻¹)	0.74
Crystal size (mm)	0.17 × 0.15 × 0.12

Data collection
Diffractometer	Bruker Kappa APEXII DUO diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	26923, 2295, 2290
R_int	0.026
(sin θ/λ)_max (Å⁻¹)	0.608

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.026, 0.078, 1.15
No. of reflections	2295
No. of parameters	172
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.17, −0.16
Absolute structure	Flack (1983) and Hooft et al. (2008) [Hooft parameter = 0.00(2), (943 Bijvoet pairs)]'
Absolute structure parameter	0.00 (16)

Computer programs: APEX2 (Bruker, 2010), SAINT (Bruker, 2010), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), WinGX (Farrugia, 1999) and PLATON (Spek, 2009), publCIF (Westrip, 2010) and PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3A···O2ⁱ	0.93 (2)	1.73 (2)	2.6395 (12)	164 (2)
O1—H1A···O3ⁱⁱ	0.86 (2)	1.93 (2)	2.7716 (13)	167 (19)

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

Acknowledgements

The authors acknowledge the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for financial support. FLO and KRLF were supported by fellowships from CAPES and CNPq, respectively. RA and FC are recipients of research fellowships from CNPq.

References

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