(S)-3-Chloro-4-(4-ethyl-piperazin-1-yl)-5-[(1R,2S,5R)-2-isopropyl-5-methyl-cyclo-hex-yloxy]furan-2(5H)-one.

The title compound, C(20)H(33)ClN(2)O(3), was obtained via a tandem asymmetric Michael addition-elimination reaction of 3,4-dichloro-5-(S)-(l-menth-yloxy)furan-2(5H)-one and 1-ethyl-piperazine in the presence of potassium fluoride. The mol-ecular structure contains an approximately planar five-membered furan-one ring [maximum atomic deviation = 0.024 (2) Å] and two six-membered rings adopting chair conformations. Weak inter-molecular C-H⋯O hydrogen bonding is present in the crystal structure.

Related literature

The title compound is a 4-amino-2(5H)-furan­one derivative. For the biological activity of 4-amino-2(5H)-furan­ones, see: Kimura et al. (2000 ▶); Tanoury et al. (2008 ▶). For the asymmetric Michael addition reactions of 2(5H)-furan­ones, see: Bertrand et al. (2000 ▶); He et al. (2006 ▶); Sarma et al. (2007 ▶). For the synthesis of the title compound, see: Song et al. (2009 ▶).

Experimental

Crystal data

C20H33ClN2O3

M = 384.93

Orthorhombic,

a = 8.7168 (15) Å

b = 10.1470 (18) Å

c = 24.478 (4) Å

V = 2165.1 (6) Å3

Z = 4

Mo Kα radiation

μ = 0.20 mm−1

T = 298 K

0.23 × 0.20 × 0.16 mm

Data collection

Bruker APEXII area-detector diffractometer

Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T min = 0.956, T max = 0.969

12202 measured reflections

4384 independent reflections

2730 reflections with I > 2σ(I)

R int = 0.045

Refinement

R[F 2 > 2σ(F 2)] = 0.046

wR(F 2) = 0.107

S = 1.01

4384 reflections

240 parameters

H-atom parameters constrained

Δρmax = 0.13 e Å−3

Δρmin = −0.17 e Å−3

Absolute structure: Flack (1983 ▶), 1866 Friedel pairs

Flack parameter: 0.00 (8)

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT (Bruker, 2008 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97.

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810026929/xu2787sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810026929/xu2787Isup2.hkl

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

C20H33ClN2O3	F(000) = 832.0
Mr = 384.93	Dx = 1.181 Mg m−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 1893 reflections
a = 8.7168 (15) Å	θ = 2.6–19.0°
b = 10.1470 (18) Å	µ = 0.20 mm−1
c = 24.478 (4) Å	T = 298 K
V = 2165.1 (6) Å3	Block, colourless
Z = 4	0.23 × 0.20 × 0.16 mm

Bruker APEXII area-detector diffractometer	4384 independent reflections
Radiation source: fine-focus sealed tube	2730 reflections with I > 2σ(I)
graphite	Rint = 0.045
φ and ω scan	θmax = 26.3°, θmin = 1.7°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −10→10
Tmin = 0.956, Tmax = 0.969	k = −8→12
12202 measured reflections	l = −30→30

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)] = 0.046	H-atom parameters constrained
wR(F2) = 0.107	w = 1/[σ2(Fo2) + (0.0425P)2 + 0.0387P] where P = (Fo2 + 2Fc2)/3
S = 1.01	(Δ/σ)max < 0.001
4384 reflections	Δρmax = 0.13 e Å−3
240 parameters	Δρmin = −0.17 e Å−3
0 restraints	Absolute structure: Flack (1983), 1866 Friedel pairs
Primary atom site location: structure-invariant direct methods	Flack parameter: 0.00 (8)

Experimental. Data for (I): [α]20°D = -32.5° (c 0.452, CH3CH2OH); 1H NMR (400 MHz, CDCl3, TMS): 0.720 (3H, d, J = 6.8 Hz, CH3), 0.766-1.142 (12H, m, CH, CH2, 3CH3), 1.221-1.388 (2H, m, 2CH), 1.611-1.660 (2H, m, CH2), 2.103-2.227 (2H, m, CH2), 2.435 (2H, d, J = 7.2 Hz, CH2), 2.495-2.515 (4H, m, 2CH2), 3.484-3.548 (1H, ddd, J = 4.4 Hz, J = 4.4 Hz,J = 4.4 Hz,CH), 3.591-3.624 (2H, m, CH2), 3.729-3.761 (2H, m, CH2), 5.751 (1H, s, CH), ESI-MS, m/z (%): Calcd for C20H34ClN2O3+([M+H]+): 385.22, Found: 385.39 (72.0).

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 > 2sigma(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
Cl1	0.92355 (9)	−0.19339 (9)	0.15783 (3)	0.0824 (3)
C1	1.0114 (3)	−0.1277 (3)	0.25997 (11)	0.0600 (7)
C2	0.8953 (3)	−0.1150 (3)	0.21895 (10)	0.0527 (7)
C3	0.7814 (3)	−0.0351 (2)	0.23643 (9)	0.0464 (6)
C4	0.8249 (3)	0.0073 (3)	0.29384 (9)	0.0486 (6)
H4	0.8300	0.1035	0.2967	0.058*
C5	0.7051 (3)	0.0215 (3)	0.38183 (9)	0.0526 (6)
H5	0.6699	0.1120	0.3756	0.063*
C6	0.5819 (3)	−0.0524 (3)	0.41368 (10)	0.0604 (7)
H6	0.6217	−0.1414	0.4200	0.072*
C7	0.5633 (4)	0.0115 (4)	0.46984 (11)	0.0893 (10)
H7A	0.5220	0.0997	0.4653	0.107*
H7B	0.4903	−0.0391	0.4911	0.107*
C8	0.7140 (4)	0.0195 (4)	0.50074 (12)	0.1017 (12)
H8A	0.6975	0.0648	0.5351	0.122*
H8B	0.7494	−0.0690	0.5089	0.122*
C9	0.8364 (4)	0.0913 (4)	0.46850 (12)	0.0842 (10)
H9	0.8015	0.1820	0.4626	0.101*
C11	0.9897 (4)	0.0966 (4)	0.49839 (12)	0.1230 (15)
H11A	0.9775	0.1439	0.5321	0.185*
H11B	1.0640	0.1407	0.4760	0.185*
H11C	1.0241	0.0086	0.5060	0.185*
C12	0.4297 (3)	−0.0685 (3)	0.38336 (12)	0.0701 (8)
H12	0.4543	−0.1031	0.3470	0.084*
C13	0.3255 (4)	−0.1697 (4)	0.41080 (14)	0.1061 (13)
H13A	0.3810	−0.2504	0.4161	0.159*
H13B	0.2378	−0.1859	0.3880	0.159*
H13C	0.2921	−0.1365	0.4455	0.159*
C14	0.3423 (4)	0.0598 (4)	0.37461 (14)	0.0934 (11)
H14A	0.2544	0.0436	0.3519	0.140*
H14B	0.4081	0.1229	0.3571	0.140*
H14C	0.3092	0.0938	0.4093	0.140*
N2	0.6474 (2)	0.0035 (2)	0.21506 (8)	0.0520 (5)
C15	0.5990 (3)	−0.0392 (3)	0.16045 (10)	0.0684 (8)
H15A	0.6371	−0.1275	0.1535	0.082*
H15B	0.6425	0.0192	0.1332	0.082*
C16	0.4266 (3)	−0.0384 (3)	0.15570 (10)	0.0656 (8)
H16A	0.3968	−0.0654	0.1192	0.079*
H16B	0.3831	−0.1005	0.1815	0.079*
N1	0.3681 (2)	0.0924 (2)	0.16674 (9)	0.0557 (6)
C17	0.4034 (3)	0.1223 (3)	0.22317 (10)	0.0628 (8)
H17A	0.3579	0.0559	0.2466	0.075*
H17B	0.3591	0.2069	0.2328	0.075*
C18	0.5741 (3)	0.1263 (2)	0.23249 (11)	0.0581 (7)
H18A	0.6178	0.1995	0.2123	0.070*
H18B	0.5944	0.1406	0.2710	0.070*
C19	0.2032 (3)	0.1040 (3)	0.15658 (12)	0.0750 (9)
H19A	0.1686	0.1891	0.1698	0.090*
H19B	0.1503	0.0367	0.1774	0.090*
C20	0.1589 (4)	0.0909 (4)	0.09789 (13)	0.0967 (12)
H20A	0.2230	0.1468	0.0760	0.145*
H20B	0.0536	0.1165	0.0934	0.145*
H20C	0.1715	0.0010	0.0865	0.145*
O3	0.71812 (18)	−0.04391 (16)	0.32993 (6)	0.0511 (4)
O1	0.97260 (19)	−0.05115 (19)	0.30335 (7)	0.0606 (5)
O2	1.1286 (2)	−0.1903 (2)	0.25964 (9)	0.0842 (7)
C10	0.8549 (3)	0.0261 (3)	0.41285 (10)	0.0655 (8)
H10A	0.9300	0.0747	0.3916	0.079*
H10B	0.8931	−0.0629	0.4178	0.079*

	U11	U22	U33	U12	U13	U23
Cl1	0.0705 (5)	0.0943 (6)	0.0825 (5)	0.0125 (5)	0.0059 (4)	−0.0335 (5)
C1	0.0460 (16)	0.0667 (19)	0.0674 (18)	−0.0018 (15)	0.0059 (15)	−0.0001 (15)
C2	0.0478 (16)	0.0528 (17)	0.0576 (16)	0.0012 (14)	0.0048 (13)	−0.0056 (13)
C3	0.0434 (14)	0.0465 (16)	0.0492 (14)	−0.0033 (13)	0.0018 (12)	0.0005 (12)
C4	0.0420 (14)	0.0505 (16)	0.0532 (15)	0.0018 (12)	0.0031 (11)	0.0020 (13)
C5	0.0592 (16)	0.0538 (16)	0.0448 (14)	0.0042 (15)	0.0001 (12)	−0.0004 (13)
C6	0.0641 (18)	0.0607 (17)	0.0564 (16)	0.0063 (16)	0.0095 (14)	0.0025 (14)
C7	0.092 (2)	0.120 (3)	0.0563 (18)	0.002 (2)	0.0142 (17)	−0.0032 (19)
C8	0.109 (3)	0.148 (4)	0.0476 (17)	0.007 (3)	0.0026 (19)	0.005 (2)
C9	0.091 (2)	0.104 (3)	0.0579 (19)	0.005 (2)	−0.0121 (17)	−0.0102 (19)
C11	0.114 (3)	0.186 (4)	0.069 (2)	−0.008 (3)	−0.029 (2)	−0.019 (3)
C12	0.0611 (19)	0.076 (2)	0.0736 (18)	−0.0031 (18)	0.0139 (16)	−0.0076 (17)
C13	0.092 (3)	0.111 (3)	0.115 (3)	−0.026 (2)	0.037 (2)	−0.002 (2)
C14	0.069 (2)	0.111 (3)	0.101 (3)	0.019 (2)	0.0029 (18)	−0.004 (2)
N2	0.0535 (13)	0.0548 (13)	0.0477 (12)	0.0074 (11)	−0.0039 (9)	−0.0076 (10)
C15	0.074 (2)	0.079 (2)	0.0519 (16)	0.0173 (17)	−0.0076 (14)	−0.0158 (15)
C16	0.0697 (19)	0.069 (2)	0.0585 (16)	0.0001 (17)	−0.0149 (15)	−0.0098 (15)
N1	0.0487 (13)	0.0603 (15)	0.0582 (13)	0.0017 (11)	−0.0077 (10)	−0.0035 (12)
C17	0.0540 (17)	0.070 (2)	0.0643 (18)	0.0115 (15)	−0.0043 (14)	−0.0135 (15)
C18	0.0570 (16)	0.0541 (17)	0.0631 (16)	0.0097 (14)	−0.0130 (14)	−0.0084 (14)
C19	0.0573 (18)	0.090 (2)	0.077 (2)	−0.0004 (17)	−0.0157 (16)	−0.0069 (18)
C20	0.083 (2)	0.113 (3)	0.094 (2)	0.000 (2)	−0.0368 (19)	0.008 (2)
O3	0.0510 (10)	0.0557 (11)	0.0465 (9)	−0.0049 (9)	0.0040 (8)	−0.0008 (8)
O1	0.0435 (10)	0.0781 (13)	0.0601 (11)	0.0085 (10)	−0.0047 (8)	−0.0019 (10)
O2	0.0541 (12)	0.0954 (16)	0.1032 (17)	0.0258 (12)	−0.0054 (11)	−0.0103 (14)
C10	0.0653 (18)	0.079 (2)	0.0524 (16)	−0.0018 (17)	−0.0031 (13)	0.0017 (15)

Cl1—C2	1.712 (2)	C12—H12	0.9800
C1—O2	1.203 (3)	C13—H13A	0.9600
C1—O1	1.358 (3)	C13—H13B	0.9600
C1—C2	1.431 (4)	C13—H13C	0.9600
C2—C3	1.351 (3)	C14—H14A	0.9600
C3—N2	1.338 (3)	C14—H14B	0.9600
C3—C4	1.518 (3)	C14—H14C	0.9600
C4—O3	1.384 (3)	N2—C18	1.463 (3)
C4—O1	1.437 (3)	N2—C15	1.468 (3)
C4—H4	0.9800	C15—C16	1.507 (4)
C5—O3	1.438 (3)	C15—H15A	0.9700
C5—C10	1.511 (3)	C15—H15B	0.9700
C5—C6	1.524 (4)	C16—N1	1.447 (3)
C5—H5	0.9800	C16—H16A	0.9700
C6—C7	1.529 (4)	C16—H16B	0.9700
C6—C12	1.529 (4)	N1—C17	1.447 (3)
C6—H6	0.9800	N1—C19	1.463 (3)
C7—C8	1.518 (4)	C17—C18	1.506 (3)
C7—H7A	0.9700	C17—H17A	0.9700
C7—H7B	0.9700	C17—H17B	0.9700
C8—C9	1.514 (5)	C18—H18A	0.9700
C8—H8A	0.9700	C18—H18B	0.9700
C8—H8B	0.9700	C19—C20	1.494 (4)
C9—C10	1.523 (4)	C19—H19A	0.9700
C9—C11	1.524 (4)	C19—H19B	0.9700
C9—H9	0.9800	C20—H20A	0.9600
C11—H11A	0.9600	C20—H20B	0.9600
C11—H11B	0.9600	C20—H20C	0.9600
C11—H11C	0.9600	C10—H10A	0.9700
C12—C14	1.524 (4)	C10—H10B	0.9700
C12—C13	1.527 (4)
O2—C1—O1	121.2 (3)	C12—C13—H13C	109.5
O2—C1—C2	130.0 (3)	H13A—C13—H13C	109.5
O1—C1—C2	108.7 (2)	H13B—C13—H13C	109.5
C3—C2—C1	110.6 (2)	C12—C14—H14A	109.5
C3—C2—Cl1	131.4 (2)	C12—C14—H14B	109.5
C1—C2—Cl1	118.0 (2)	H14A—C14—H14B	109.5
N2—C3—C2	133.9 (2)	C12—C14—H14C	109.5
N2—C3—C4	119.8 (2)	H14A—C14—H14C	109.5
C2—C3—C4	106.2 (2)	H14B—C14—H14C	109.5
O3—C4—O1	110.14 (19)	C3—N2—C18	121.1 (2)
O3—C4—C3	108.46 (19)	C3—N2—C15	121.4 (2)
O1—C4—C3	104.89 (19)	C18—N2—C15	113.0 (2)
O3—C4—H4	111.1	N2—C15—C16	110.8 (2)
O1—C4—H4	111.1	N2—C15—H15A	109.5
C3—C4—H4	111.1	C16—C15—H15A	109.5
O3—C5—C10	113.0 (2)	N2—C15—H15B	109.5
O3—C5—C6	106.3 (2)	C16—C15—H15B	109.5
C10—C5—C6	111.5 (2)	H15A—C15—H15B	108.1
O3—C5—H5	108.6	N1—C16—C15	110.0 (2)
C10—C5—H5	108.6	N1—C16—H16A	109.7
C6—C5—H5	108.6	C15—C16—H16A	109.7
C5—C6—C7	109.0 (2)	N1—C16—H16B	109.7
C5—C6—C12	114.6 (2)	C15—C16—H16B	109.7
C7—C6—C12	112.9 (2)	H16A—C16—H16B	108.2
C5—C6—H6	106.6	C17—N1—C16	107.2 (2)
C7—C6—H6	106.6	C17—N1—C19	110.7 (2)
C12—C6—H6	106.6	C16—N1—C19	112.9 (2)
C8—C7—C6	112.2 (3)	N1—C17—C18	111.1 (2)
C8—C7—H7A	109.2	N1—C17—H17A	109.4
C6—C7—H7A	109.2	C18—C17—H17A	109.4
C8—C7—H7B	109.2	N1—C17—H17B	109.4
C6—C7—H7B	109.2	C18—C17—H17B	109.4
H7A—C7—H7B	107.9	H17A—C17—H17B	108.0
C9—C8—C7	112.1 (3)	N2—C18—C17	111.4 (2)
C9—C8—H8A	109.2	N2—C18—H18A	109.4
C7—C8—H8A	109.2	C17—C18—H18A	109.4
C9—C8—H8B	109.2	N2—C18—H18B	109.4
C7—C8—H8B	109.2	C17—C18—H18B	109.4
H8A—C8—H8B	107.9	H18A—C18—H18B	108.0
C8—C9—C10	109.4 (3)	N1—C19—C20	114.2 (3)
C8—C9—C11	112.6 (3)	N1—C19—H19A	108.7
C10—C9—C11	110.6 (3)	C20—C19—H19A	108.7
C8—C9—H9	108.0	N1—C19—H19B	108.7
C10—C9—H9	108.0	C20—C19—H19B	108.7
C11—C9—H9	108.0	H19A—C19—H19B	107.6
C9—C11—H11A	109.5	C19—C20—H20A	109.5
C9—C11—H11B	109.5	C19—C20—H20B	109.5
H11A—C11—H11B	109.5	H20A—C20—H20B	109.5
C9—C11—H11C	109.5	C19—C20—H20C	109.5
H11A—C11—H11C	109.5	H20A—C20—H20C	109.5
H11B—C11—H11C	109.5	H20B—C20—H20C	109.5
C14—C12—C13	109.8 (3)	C4—O3—C5	116.3 (2)
C14—C12—C6	114.3 (3)	C1—O1—C4	109.41 (19)
C13—C12—C6	112.0 (3)	C5—C10—C9	111.8 (2)
C14—C12—H12	106.8	C5—C10—H10A	109.3
C13—C12—H12	106.8	C9—C10—H10A	109.3
C6—C12—H12	106.8	C5—C10—H10B	109.3
C12—C13—H13A	109.5	C9—C10—H10B	109.3
C12—C13—H13B	109.5	H10A—C10—H10B	107.9
H13A—C13—H13B	109.5

D—H···A	D—H	H···A	D···A	D—H···A
C4—H4···O2i	0.98	2.53	3.361 (4)	142

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C4—H4⋯O2i	0.98	2.53	3.361 (4)	142

Symmetry code: (i) .