(1S,2S,6R,7aR)-2-Benzyl-1,6-dihy-droxy-hexa-hydro-pyrrolizin-3-one.

In the title compound, C(14)H(17)NO(3), 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 = 247.29

Orthorhombic,

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[F 2 > 2σ(F 2)] = 0.026

wR(F 2) = 0.078

S = 1.15

2295 reflections

172 parameters

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.17 e Å−3

Δρmin = −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)

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.

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812002334/pv2494sup1.cif

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

Supplementary material file. DOI: 10.1107/S1600536812002334/pv2494Isup3.cml

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

C14H17NO3	Dx = 1.297 Mg m−3
Mr = 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

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

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(Fo2) + (0.0491P)2 + 0.1808P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.078	(Δ/σ)max = 0.001
S = 1.15	Δρmax = 0.17 e Å−3
2295 reflections	Δρmin = −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	Flack parameter: 0.00 (16)

Experimental. [α]D20 + 51 (c 1, MeOH); M. p. 135–136° C; IR (KBr, vmax): 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, JH3,H4 = 7.0, J = 8.0, 5.3 Hz, 1H, H-3); 3.88 (dd,JH4,H5 = 9.4, JH3,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.

	x	y	z	Uiso*/Ueq
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)*

	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)

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

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)

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) ; (ii) .