Ethyl 1-benzyl-4-hydr-oxy-2-methyl-5-oxopyrrolidine-3-carboxyl-ate.

In the title oxopyrrolidine, C(15)H(19)NO(4), the five-membered pyrrolidine ring is in a twist conformation and its mean plane makes an angle of 89.2 (3)° with the phenyl ring. In the crystal, mol-ecules pack as dimers via strong O-H⋯O [R(2) (2)(10)] inter-actions cross-linked by weaker C-H⋯O and C-H⋯π inter-actions. Full synthetic and spectroscopic details are given for the title compound and related dicarboxyl-ates.

Related literature

For details of a programme to elucidate the structure–activity relationships of the Immucillin family of potent purine nucleoside phospho­rylase inhibitors, see: Mason et al. (2007 ▶); Edwards et al. (2009 ▶); Clinch et al. (2009 ▶). For a related structure, see: Snider et al. (2000 ▶). For ring conformations see: Cremer & Pople (1975 ▶) and for hydrogen-bond motifs, see: Bernstein et al. (1995 ▶).

Experimental

Crystal data

C15H19NO4

M = 277.31

Orthorhombic,

a = 27.746 (12) Å

b = 14.035 (5) Å

c = 7.357 (3) Å

V = 2865 (2) Å3

Z = 8

Mo Kα radiation

μ = 0.09 mm−1

T = 93 K

0.45 × 0.14 × 0.01 mm

Data collection

Siemens SMART APEX CCD area-detector diffractometer

9428 measured reflections

2376 independent reflections

531 reflections with I > 2σ(I)

R int = 0.136

Refinement

R[F 2 > 2σ(F 2)] = 0.049

wR(F 2) = 0.138

S = 1.10

2376 reflections

146 parameters

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.26 e Å−3

Δρmin = −0.21 e Å−3

Data collection: SMART (Siemens, 1996 ▶); cell refinement: SAINT (Siemens, 1996 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP in WinGX (Farrugia, 1997 ▶) and Mercury (Macrae et al., 2006 ▶); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009 ▶).

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810010834/sj2755sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810010834/sj2755Isup2.hkl

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

C15H19NO4	F(000) = 1184
Mr = 277.31	Dx = 1.286 Mg m−3
Orthorhombic, Pbca	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 708 reflections
a = 27.746 (12) Å	θ = 2.9–17.8°
b = 14.035 (5) Å	µ = 0.09 mm−1
c = 7.357 (3) Å	T = 93 K
V = 2865 (2) Å3	Plate, colourless
Z = 8	0.45 × 0.14 × 0.01 mm

Bruker APEXII CCD area-detector diffractometer	531 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.136
graphite	θmax = 25.0°, θmin = 2.9°
Detector resolution: 8.333 pixels mm-1	h = −32→32
φ and ω scans	k = −16→16
9428 measured reflections	l = −7→7
2376 independent reflections

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.049	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.138	H atoms treated by a mixture of independent and constrained refinement
S = 1.10	[exp(7.00(sinθ/λ)2)]/[σ2(Fo2) + (0.010P)2], where P = 0.33333Fo2 + 0.66667Fc2
2376 reflections	(Δ/σ)max < 0.001
146 parameters	Δρmax = 0.26 e Å−3
0 restraints	Δρmin = −0.21 e Å−3

Experimental. (I)(2S*,3S*,4R*)-Ethyl-1-benzyl-4-hydroxy-2-methyl -5-oxopyrrolidine-3-carboxylate (I) 1H NMR (300 MHz, CDCl3, TMS) δ 7.35-7.20 (m, 5H), 4.97 (d, J = 15.1 Hz, 1H), 4.64 (d, J = 8.7 Hz, 1H), 4.18 (q, J = 7.1 Hz, 2H), 4.07 (d, J = 15.1 Hz, 1H),3.83 (bs, 1H), 3.56 (m, 1H), 2.71 (t, J = 8.7 Hz, 1H), 1.33-1.06 (m, 6H). 13C NMR (CDCl3, 75.5 MHz, centre line of solvent 77.4 ppm) 173.2, 171.6, 136.0, 129.2, 128.3, 128.2, 72.5, 61.9, 54.7, 52.6, 44.6, 19.4, 14.5.(II) (3S*,4S*,5R*)-Diethyl 2-benzyl-3-methylisoxazolidine-4,5-dicarboxylate 1H NMR (300 MHz, CDCl3, TMS) δ 7.39-7.12 (m, 5H), 4.58 (d, J = 8.4 Hz, 1H), 4.17-3.96 (m, 6H), 3.26 (m, 2H), 1.18 (m, 9H). 13C NMR (CDCl3, 75.5 MHz, centre line of solvent 77.4 ppm) 169.2, 169.0, 137.0, 128.7, 128.1, 127.1, 75.8, 63.8, 60.8, 60.2, 57.4, 16.2, 13.6.(III) (3R*,4S*,5R*)-Diethyl 2-benzyl-3-methylisoxazolidine-4,5-dicarboxylate 1H NMR (300 MHz, CDCl3, TMS) δ 7.52-7.21 (m, 5H), 4.74 (d, J = 9.2 Hz, 1H), 4.32-4.05 (m, 5H), 3.95 (d, J = 14.3 Hz, 1H), 3.85 (dd, J = 7.6, 9.1 Hz, 1H), 3.30 (m, 1H), 1.86-1.11 (m, 9H). 13C NMR (CDCl3, 75.5 MHz, centre line of solvent 77.4 ppm) 170.1, 169.5, 136.7, 129.3. 128.6, 127.7, 76.2, 62.6, 61.6, 61.4, 59.6, 55.1, 14.6, 14.4.

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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	0.58333 (18)	0.5432 (2)	0.5104 (6)	0.0312 (13)
O2	0.4974 (2)	0.5137 (3)	0.2899 (6)	0.0249 (12)
H2O	0.470 (2)	0.490 (4)	0.347 (7)	0.030*
O3	0.55079 (18)	0.2657 (3)	−0.0461 (7)	0.0352 (14)
O4	0.48229 (16)	0.3345 (3)	0.0499 (6)	0.0229 (11)*
N1	0.6190 (2)	0.4824 (3)	0.2531 (7)	0.0215 (14)
C1	0.6322 (3)	0.4387 (4)	−0.0757 (8)	0.036 (2)
H1A	0.6672	0.4340	−0.0602	0.053*
H1B	0.6237	0.5038	−0.1119	0.053*
H1C	0.6218	0.3939	−0.1700	0.053*
C2	0.6070 (2)	0.4141 (4)	0.1053 (9)	0.0195 (16)*
H2	0.6166	0.3484	0.1436	0.023*
C3	0.5537 (2)	0.4208 (4)	0.0992 (9)	0.0234 (17)*
H3	0.5456	0.4744	0.0151	0.028*
C4	0.5375 (2)	0.4506 (4)	0.2884 (8)	0.0203 (17)
H4	0.5295	0.3925	0.3612	0.024*
C5	0.5818 (3)	0.4975 (4)	0.3670 (9)	0.0216 (15)*
C6	0.5296 (2)	0.3317 (4)	0.0232 (9)	0.0210 (16)*
C7	0.4550 (2)	0.2497 (4)	−0.0061 (11)	0.0313 (19)
H7A	0.4625	0.1952	0.0744	0.038*
H7B	0.4632	0.2319	−0.1326	0.038*
C8	0.4022 (2)	0.2757 (4)	0.0083 (11)	0.034 (2)
H8A	0.3950	0.3279	−0.0760	0.051*
H8B	0.3950	0.2960	0.1329	0.051*
H8C	0.3825	0.2202	−0.0225	0.051*
C9	0.6675 (2)	0.5142 (4)	0.2908 (9)	0.0278 (19)
H9A	0.6664	0.5596	0.3938	0.033*
H9B	0.6797	0.5493	0.1835	0.033*
C10	0.7025 (2)	0.4361 (4)	0.3362 (9)	0.0204 (16)*
C11	0.7490 (3)	0.4379 (4)	0.2743 (9)	0.0260 (16)*
H11	0.7583	0.4889	0.1969	0.031*
C12	0.7833 (3)	0.3696 (4)	0.3179 (8)	0.0238 (17)*
H12	0.8155	0.3733	0.2747	0.029*
C13	0.7674 (3)	0.2941 (4)	0.4305 (10)	0.033 (2)
H13	0.7897	0.2458	0.4641	0.039*
C14	0.7214 (3)	0.2886 (4)	0.4920 (11)	0.031 (2)
H14	0.7116	0.2362	0.5647	0.037*
C15	0.6886 (3)	0.3600 (4)	0.4480 (8)	0.0318 (19)
H15	0.6566	0.3572	0.4941	0.038*

	U11	U22	U33	U12	U13	U23
O1	0.057 (4)	0.0099 (18)	0.026 (3)	0.003 (2)	−0.001 (3)	−0.002 (2)
O2	0.042 (3)	0.0100 (19)	0.023 (3)	0.002 (2)	0.006 (3)	0.0030 (19)
O3	0.044 (3)	0.012 (2)	0.050 (3)	0.002 (2)	0.006 (3)	−0.012 (2)
N1	0.033 (4)	0.014 (2)	0.017 (3)	−0.002 (2)	0.002 (3)	−0.006 (2)
C1	0.049 (6)	0.026 (3)	0.032 (4)	−0.005 (4)	−0.003 (5)	0.001 (4)
C4	0.032 (5)	0.014 (3)	0.014 (4)	0.000 (3)	0.002 (4)	0.002 (3)
C7	0.039 (5)	0.010 (2)	0.046 (5)	−0.001 (3)	−0.007 (5)	0.009 (3)
C8	0.041 (5)	0.016 (3)	0.046 (5)	−0.006 (3)	−0.002 (5)	−0.004 (4)
C9	0.035 (5)	0.013 (3)	0.035 (5)	−0.006 (3)	0.001 (4)	−0.004 (3)
C13	0.044 (5)	0.014 (3)	0.039 (5)	0.006 (3)	−0.005 (5)	−0.010 (3)
C14	0.036 (5)	0.021 (3)	0.036 (5)	−0.003 (3)	−0.001 (5)	0.012 (4)
C15	0.047 (5)	0.021 (3)	0.028 (4)	−0.012 (3)	0.000 (5)	−0.008 (3)

O1—C5	1.236 (7)	C7—C8	1.512 (8)
O2—C4	1.421 (7)	C7—H7A	0.9900
O2—H2O	0.94 (6)	C7—H7B	0.9900
O3—C6	1.211 (7)	C8—H8A	0.9800
O4—C6	1.328 (7)	C8—H8B	0.9800
O4—C7	1.471 (6)	C8—H8C	0.9800
N1—C5	1.346 (8)	C9—C10	1.504 (8)
N1—C9	1.442 (8)	C9—H9A	0.9900
N1—C2	1.488 (7)	C9—H9B	0.9900
C1—C2	1.543 (8)	C10—C11	1.367 (9)
C1—H1A	0.9800	C10—C15	1.402 (8)
C1—H1B	0.9800	C11—C12	1.389 (8)
C1—H1C	0.9800	C11—H11	0.9500
C5—C4	1.511 (8)	C12—C13	1.414 (8)
C4—C3	1.522 (8)	C12—H12	0.9500
C4—H4	1.0000	C13—C14	1.357 (9)
C3—C2	1.484 (9)	C13—H13	0.9500
C3—C6	1.523 (8)	C14—C15	1.392 (9)
C3—H3	1.0000	C14—H14	0.9500
C2—H2	1.0000	C15—H15	0.9500
C4—O2—H2O	115 (4)	O4—C7—H7A	110.4
C6—O4—C7	116.4 (5)	C8—C7—H7A	110.4
C5—N1—C9	123.1 (6)	O4—C7—H7B	110.4
C5—N1—C2	112.6 (5)	C8—C7—H7B	110.4
C9—N1—C2	123.3 (5)	H7A—C7—H7B	108.6
C2—C1—H1A	109.5	C7—C8—H8A	109.5
C2—C1—H1B	109.5	C7—C8—H8B	109.5
H1A—C1—H1B	109.5	H8A—C8—H8B	109.5
C2—C1—H1C	109.5	C7—C8—H8C	109.5
H1A—C1—H1C	109.5	H8A—C8—H8C	109.5
H1B—C1—H1C	109.5	H8B—C8—H8C	109.5
O1—C5—N1	126.0 (7)	N1—C9—C10	114.8 (5)
O1—C5—C4	125.5 (7)	N1—C9—H9A	108.6
N1—C5—C4	108.6 (5)	C10—C9—H9A	108.6
O2—C4—C5	111.3 (5)	N1—C9—H9B	108.6
O2—C4—C3	114.2 (5)	C10—C9—H9B	108.6
C5—C4—C3	103.2 (6)	H9A—C9—H9B	107.5
O2—C4—H4	109.3	C11—C10—C15	118.0 (6)
C5—C4—H4	109.3	C11—C10—C9	121.5 (6)
C3—C4—H4	109.3	C15—C10—C9	120.5 (7)
C2—C3—C4	106.5 (6)	C10—C11—C12	123.8 (6)
C2—C3—C6	113.4 (5)	C10—C11—H11	118.1
C4—C3—C6	115.6 (6)	C12—C11—H11	118.1
C2—C3—H3	106.9	C11—C12—C13	116.1 (7)
C4—C3—H3	106.9	C11—C12—H12	122.0
C6—C3—H3	106.9	C13—C12—H12	122.0
C3—C2—N1	101.8 (5)	C14—C13—C12	122.0 (7)
C3—C2—C1	114.3 (6)	C14—C13—H13	119.0
N1—C2—C1	112.6 (5)	C12—C13—H13	119.0
C3—C2—H2	109.3	C13—C14—C15	119.8 (7)
N1—C2—H2	109.3	C13—C14—H14	120.1
C1—C2—H2	109.3	C15—C14—H14	120.1
O3—C6—O4	124.4 (6)	C14—C15—C10	120.3 (7)
O3—C6—C3	124.7 (6)	C14—C15—H15	119.9
O4—C6—C3	110.8 (5)	C10—C15—H15	119.9
O4—C7—C8	106.5 (5)
C9—N1—C5—O1	3.8 (10)	C7—O4—C6—O3	1.4 (10)
C2—N1—C5—O1	172.5 (6)	C7—O4—C6—C3	−176.0 (5)
C9—N1—C5—C4	−177.3 (5)	C2—C3—C6—O3	−8.4 (10)
C2—N1—C5—C4	−8.6 (7)	C4—C3—C6—O3	−131.8 (7)
O1—C5—C4—O2	47.3 (8)	C2—C3—C6—O4	169.1 (6)
N1—C5—C4—O2	−131.6 (5)	C4—C3—C6—O4	45.7 (8)
O1—C5—C4—C3	170.2 (6)	C6—O4—C7—C8	−170.9 (6)
N1—C5—C4—C3	−8.7 (6)	C5—N1—C9—C10	108.7 (6)
O2—C4—C3—C2	143.4 (5)	C2—N1—C9—C10	−58.8 (8)
C5—C4—C3—C2	22.5 (6)	N1—C9—C10—C11	140.9 (6)
O2—C4—C3—C6	−89.6 (7)	N1—C9—C10—C15	−40.8 (9)
C5—C4—C3—C6	149.5 (5)	C15—C10—C11—C12	−1.0 (10)
C4—C3—C2—N1	−26.7 (6)	C9—C10—C11—C12	177.4 (6)
C6—C3—C2—N1	−155.0 (5)	C10—C11—C12—C13	1.2 (10)
C4—C3—C2—C1	−148.5 (5)	C11—C12—C13—C14	0.2 (10)
C6—C3—C2—C1	83.3 (7)	C12—C13—C14—C15	−1.7 (11)
C5—N1—C2—C3	22.5 (7)	C13—C14—C15—C10	1.9 (11)
C9—N1—C2—C3	−168.9 (6)	C11—C10—C15—C14	−0.6 (9)
C5—N1—C2—C1	145.4 (5)	C9—C10—C15—C14	−179.0 (6)
C9—N1—C2—C1	−46.0 (8)

Cg is the centroid of the C10–C15 ring.

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2O···O1i	0.93 (5)	1.87 (5)	2.795 (7)	171 (4)
C7—H7B···O4ii	0.99	2.57	3.555 (9)	173
C4—H4···O3iii	1.0	2.40	3.292 (7)	149
C14—H14···Cg1ii	0.95	2.81	3.612 (8)	142

Table 1

Hydrogen-bond geometry (Å, °)

Cg is the centroid of the C10–C15 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2O⋯O1i	0.93 (5)	1.87 (5)	2.795 (7)	171 (4)
C7—H7B⋯O4ii	0.99	2.57	3.555 (9)	173
C4—H4⋯O3iii	1.0	2.40	3.292 (7)	149
C14—H14⋯Cg1ii	0.95	2.81	3.612 (8)	142

Symmetry codes: (i) ; (ii) ; (iii) .