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

The title compound, C(20)H(32)ClNO(3), was obtained via a tandem asymmetric Michael addition-elimination reaction of (5S)-3,4-dichloro-5-(l-menth-yloxy)furan-2(5H)-one and 4-methyl-piperidine in the presence of potassium fluoride. The furan-one ring is approximately planar [maximum atomic deviation = 0.022 (2) Å] while the cyclo-hexane ring adopts a chair conformation. Weak inter-molecular C-H⋯O hydrogen bonding is present in the crystal structure.

Related literature

The title compound is a derivative of 4-amino-2(5H)-furan­one. For the biological activity of 4-amino-2(5H)-furan­ones, see: Lattmann et al. (2005 ▶); Prasad & Gandi (2010 ▶); Steenackers et al. (2010 ▶). For asymmetric Michael addition reactions of 2(5H)-furan­one and for the synthesis of the title compound, see: Song et al. (2009 ▶).

Experimental

Crystal data

C20H32ClNO3

M = 369.92

Orthorhombic,

a = 9.187 (5) Å

b = 9.248 (5) Å

c = 24.987 (12) Å

V = 2122.9 (19) Å3

Z = 4

Mo Kα radiation

μ = 0.20 mm−1

T = 298 K

0.32 × 0.30 × 0.28 mm

Data collection

Bruker APEXII area-detector diffractometer

Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T min = 0.940, T max = 0.947

12264 measured reflections

4505 independent reflections

2620 reflections with I > 2σ(I)

R int = 0.038

Refinement

R[F 2 > 2σ(F 2)] = 0.043

wR(F 2) = 0.112

S = 1.01

4505 reflections

231 parameters

24 restraints

H-atom parameters constrained

Δρmax = 0.13 e Å−3

Δρmin = −0.16 e Å−3

Absolute structure: Flack (1983 ▶), 1921 Friedel pairs

Flack parameter: 0.10 (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/S1600536811005216/go2003sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811005216/go2003Isup2.hkl

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

C20H32ClNO3	F(000) = 800
Mr = 369.92	Dx = 1.157 Mg m−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 2408 reflections
a = 9.187 (5) Å	θ = 2.7–19.8°
b = 9.248 (5) Å	µ = 0.20 mm−1
c = 24.987 (12) Å	T = 298 K
V = 2122.9 (19) Å3	Block, colourless
Z = 4	0.32 × 0.30 × 0.28 mm

Bruker APEXII area-detector diffractometer	4505 independent reflections
Radiation source: fine-focus sealed tube	2620 reflections with I > 2σ(I)
graphite	Rint = 0.038
φ and ω scans	θmax = 26.8°, θmin = 2.4°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −10→11
Tmin = 0.940, Tmax = 0.947	k = −11→10
12264 measured reflections	l = −31→31

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)] = 0.043	H-atom parameters constrained
wR(F2) = 0.112	w = 1/[σ2(Fo2) + (0.0492P)2 + 0.001P] where P = (Fo2 + 2Fc2)/3
S = 1.01	(Δ/σ)max < 0.001
4505 reflections	Δρmax = 0.13 e Å−3
231 parameters	Δρmin = −0.16 e Å−3
24 restraints	Absolute structure: Flack (1983), 1921 Friedel pairs
Primary atom site location: structure-invariant direct methods	Flack parameter: 0.10 (8)

Experimental. Data for (I): [α]20°D = 96.2° (c 0.600, CH3CH2OH); 1H NMR (400 MHz, CDCl3, TMS): 0.769 (3H, d, J = 6.8 Hz, CH3), 0.831-0.934 (7H, m, CH, 2CH3), 0.981-1.166 (5H, m, CH2, CH3), 1.212-1.756 (9H, m, 3CH, 3CH2), 2.160-2.271 (2H, m, CH2), 2.974-3.090 (2H, m, CH2), 3.529-3.581 (1H, m, CH), 4.079-4.335 (2H, m, CH2), 5.762 (1H, s, CH), ESI-MS, m/z (%): Calcd for C20H32ClNO3+([M+H]+): 370.21(100.0), 372.20(32.0), Found: 370.29 (45.0), 372.33(15.0).

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	0.60861 (9)	−0.13528 (9)	0.17373 (3)	0.0923 (3)
C3	0.7320 (3)	0.0841 (3)	0.23600 (8)	0.0557 (6)
C4	0.8425 (3)	0.0853 (3)	0.28119 (8)	0.0578 (6)
H4	0.9252	0.1479	0.2725	0.069*
C2	0.7123 (3)	−0.0578 (3)	0.22267 (9)	0.0621 (7)
C1	0.8084 (3)	−0.1478 (4)	0.25291 (10)	0.0681 (7)
C5	0.8604 (3)	0.1414 (3)	0.37500 (8)	0.0621 (6)
H5	0.9630	0.1522	0.3650	0.074*
C6	0.8125 (3)	0.2733 (3)	0.40633 (9)	0.0702 (8)
H6	0.7085	0.2604	0.4136	0.084*
C7	0.8883 (4)	0.2751 (4)	0.46068 (10)	0.0956 (9)
H7A	0.9919	0.2897	0.4554	0.115*
H7B	0.8517	0.3558	0.4815	0.115*
C10	0.8414 (4)	0.0021 (4)	0.40651 (11)	0.0960 (11)
H10A	0.8791	−0.0780	0.3856	0.115*
H10B	0.7385	−0.0149	0.4124	0.115*
C11	0.8269 (4)	0.4160 (4)	0.37596 (11)	0.0878 (10)
H11	0.7799	0.4016	0.3412	0.105*
C9	0.9194 (5)	0.0065 (4)	0.46042 (11)	0.1115 (13)
H9	1.0238	0.0194	0.4538	0.134*
C8	0.8648 (6)	0.1363 (5)	0.49177 (11)	0.1279 (14)
H8A	0.7619	0.1245	0.4993	0.153*
H8B	0.9160	0.1419	0.5257	0.153*
C13	0.7463 (5)	0.5387 (4)	0.40314 (16)	0.1393 (16)
H13A	0.7508	0.6236	0.3811	0.209*
H13B	0.7906	0.5586	0.4371	0.209*
H13C	0.6465	0.5117	0.4084	0.209*
C14	0.9795 (6)	0.4590 (5)	0.36473 (16)	0.1399 (16)
H14A	1.0262	0.4871	0.3975	0.210*
H14B	0.9802	0.5388	0.3402	0.210*
H14C	1.0308	0.3788	0.3493	0.210*
C18	0.7583 (3)	0.4266 (3)	0.17613 (10)	0.0709 (7)
H18A	0.8318	0.3755	0.1557	0.085*
H18B	0.7946	0.5232	0.1833	0.085*
C19	0.7345 (3)	0.3499 (3)	0.22804 (9)	0.0711 (7)
H19A	0.8266	0.3401	0.2467	0.085*
H19B	0.6696	0.4065	0.2504	0.085*
C16	0.5572 (3)	0.2862 (3)	0.13592 (10)	0.0750 (8)
H16A	0.4646	0.2930	0.1174	0.090*
H16B	0.6226	0.2290	0.1140	0.090*
C15	0.5354 (3)	0.2122 (3)	0.18891 (9)	0.0691 (7)
H15A	0.4628	0.2643	0.2095	0.083*
H15B	0.4996	0.1149	0.1830	0.083*
C17	0.6204 (3)	0.4374 (3)	0.14313 (10)	0.0755 (8)
H17	0.5498	0.4957	0.1631	0.091*
C20	0.6467 (4)	0.5099 (4)	0.08935 (13)	0.1153 (13)
H20A	0.5553	0.5251	0.0716	0.173*
H20B	0.7073	0.4490	0.0676	0.173*
H20C	0.6941	0.6012	0.0948	0.173*
N1	0.6712 (2)	0.2061 (3)	0.21914 (8)	0.0635 (6)
O3	0.77190 (15)	0.13329 (19)	0.32666 (5)	0.0606 (4)
O1	0.88796 (18)	−0.0624 (2)	0.28665 (6)	0.0692 (5)
O2	0.8292 (2)	−0.2765 (3)	0.25154 (9)	0.0958 (7)
C12	0.8980 (9)	−0.1363 (5)	0.49012 (16)	0.193 (2)
H12A	0.7961	−0.1514	0.4966	0.290*
H12B	0.9489	−0.1329	0.5237	0.290*
H12C	0.9355	−0.2142	0.4688	0.290*

	U11	U22	U33	U12	U13	U23
Cl1	0.0966 (5)	0.0925 (6)	0.0878 (5)	−0.0040 (5)	−0.0238 (4)	−0.0303 (4)
C3	0.0532 (14)	0.0716 (19)	0.0423 (11)	−0.0039 (13)	0.0037 (10)	−0.0047 (12)
C4	0.0566 (14)	0.0663 (19)	0.0507 (13)	−0.0053 (12)	−0.0014 (11)	−0.0038 (12)
C2	0.0612 (16)	0.072 (2)	0.0534 (13)	−0.0043 (14)	−0.0029 (12)	−0.0094 (13)
C1	0.0596 (15)	0.077 (2)	0.0677 (16)	0.0055 (16)	0.0053 (13)	−0.0158 (17)
C5	0.0649 (16)	0.0735 (17)	0.0478 (12)	−0.0011 (14)	−0.0084 (11)	−0.0026 (13)
C6	0.0673 (16)	0.092 (2)	0.0511 (13)	0.0086 (15)	−0.0004 (12)	−0.0171 (15)
C7	0.132 (3)	0.100 (2)	0.0542 (15)	−0.003 (2)	−0.0164 (17)	−0.0124 (17)
C10	0.132 (3)	0.092 (2)	0.0633 (16)	−0.020 (2)	−0.0195 (18)	0.0117 (17)
C11	0.126 (3)	0.078 (2)	0.0596 (16)	0.022 (2)	−0.0152 (17)	−0.0160 (16)
C9	0.173 (3)	0.094 (3)	0.0678 (18)	−0.024 (3)	−0.037 (2)	0.0227 (19)
C8	0.183 (4)	0.150 (3)	0.0514 (16)	−0.022 (3)	−0.016 (2)	0.002 (2)
C13	0.161 (4)	0.120 (3)	0.137 (3)	0.055 (3)	−0.042 (3)	−0.052 (3)
C14	0.165 (4)	0.103 (3)	0.152 (3)	0.002 (3)	0.053 (3)	0.013 (3)
C18	0.0791 (18)	0.0660 (18)	0.0678 (15)	−0.0153 (14)	−0.0104 (14)	0.0016 (14)
C19	0.0835 (19)	0.0686 (19)	0.0610 (15)	−0.0105 (16)	−0.0154 (14)	−0.0090 (14)
C16	0.0752 (18)	0.084 (2)	0.0663 (16)	−0.0017 (16)	−0.0243 (13)	−0.0002 (16)
C15	0.0592 (15)	0.0720 (18)	0.0760 (17)	−0.0043 (13)	−0.0121 (13)	−0.0002 (15)
C17	0.087 (2)	0.0695 (19)	0.0700 (15)	−0.0068 (17)	−0.0108 (15)	0.0073 (15)
C20	0.144 (3)	0.112 (3)	0.091 (2)	−0.029 (2)	−0.022 (2)	0.040 (2)
N1	0.0670 (13)	0.0634 (14)	0.0601 (11)	−0.0079 (12)	−0.0147 (10)	0.0039 (11)
O3	0.0557 (9)	0.0823 (12)	0.0436 (8)	0.0034 (9)	−0.0045 (7)	−0.0074 (9)
O1	0.0577 (10)	0.0779 (13)	0.0719 (10)	0.0108 (10)	−0.0093 (9)	−0.0086 (10)
O2	0.0908 (14)	0.0731 (15)	0.1237 (17)	0.0195 (12)	−0.0096 (12)	−0.0176 (14)
C12	0.339 (7)	0.136 (4)	0.105 (3)	−0.040 (5)	−0.072 (4)	0.049 (3)

Cl1—C2	1.708 (2)	C8—H8B	0.9700
C3—N1	1.327 (3)	C13—H13A	0.9600
C3—C2	1.366 (4)	C13—H13B	0.9600
C3—C4	1.519 (3)	C13—H13C	0.9600
C4—O3	1.381 (3)	C14—H14A	0.9600
C4—O1	1.435 (3)	C14—H14B	0.9600
C4—H4	0.9800	C14—H14C	0.9600
C2—C1	1.429 (4)	C18—C19	1.495 (4)
C1—O2	1.206 (4)	C18—C17	1.514 (4)
C1—O1	1.367 (3)	C18—H18A	0.9700
C5—O3	1.458 (3)	C18—H18B	0.9700
C5—C6	1.514 (4)	C19—N1	1.468 (3)
C5—C10	1.520 (4)	C19—H19A	0.9700
C5—H5	0.9800	C19—H19B	0.9700
C6—C7	1.526 (4)	C16—C15	1.504 (3)
C6—C11	1.529 (4)	C16—C17	1.525 (4)
C6—H6	0.9800	C16—H16A	0.9700
C7—C8	1.516 (4)	C16—H16B	0.9700
C7—H7A	0.9700	C15—N1	1.460 (3)
C7—H7B	0.9700	C15—H15A	0.9700
C10—C9	1.526 (4)	C15—H15B	0.9700
C10—H10A	0.9700	C17—C20	1.521 (4)
C10—H10B	0.9700	C17—H17	0.9800
C11—C14	1.484 (5)	C20—H20A	0.9600
C11—C13	1.516 (5)	C20—H20B	0.9600
C11—H11	0.9800	C20—H20C	0.9600
C9—C8	1.519 (5)	C12—H12A	0.9600
C9—C12	1.527 (5)	C12—H12B	0.9600
C9—H9	0.9800	C12—H12C	0.9600
C8—H8A	0.9700
N1—C3—C2	133.1 (2)	C11—C13—H13B	109.5
N1—C3—C4	120.7 (2)	H13A—C13—H13B	109.5
C2—C3—C4	106.1 (2)	C11—C13—H13C	109.5
O3—C4—O1	111.37 (19)	H13A—C13—H13C	109.5
O3—C4—C3	107.47 (18)	H13B—C13—H13C	109.5
O1—C4—C3	105.0 (2)	C11—C14—H14A	109.5
O3—C4—H4	110.9	C11—C14—H14B	109.5
O1—C4—H4	110.9	H14A—C14—H14B	109.5
C3—C4—H4	110.9	C11—C14—H14C	109.5
C3—C2—C1	110.4 (2)	H14A—C14—H14C	109.5
C3—C2—Cl1	130.7 (2)	H14B—C14—H14C	109.5
C1—C2—Cl1	118.6 (2)	C19—C18—C17	112.4 (2)
O2—C1—O1	120.2 (3)	C19—C18—H18A	109.1
O2—C1—C2	131.1 (3)	C17—C18—H18A	109.1
O1—C1—C2	108.7 (3)	C19—C18—H18B	109.1
O3—C5—C6	107.9 (2)	C17—C18—H18B	109.1
O3—C5—C10	108.7 (2)	H18A—C18—H18B	107.9
C6—C5—C10	112.4 (2)	N1—C19—C18	110.9 (2)
O3—C5—H5	109.2	N1—C19—H19A	109.5
C6—C5—H5	109.2	C18—C19—H19A	109.5
C10—C5—H5	109.2	N1—C19—H19B	109.5
C5—C6—C7	109.6 (2)	C18—C19—H19B	109.5
C5—C6—C11	114.4 (2)	H19A—C19—H19B	108.0
C7—C6—C11	113.1 (2)	C15—C16—C17	111.3 (2)
C5—C6—H6	106.3	C15—C16—H16A	109.4
C7—C6—H6	106.3	C17—C16—H16A	109.4
C11—C6—H6	106.3	C15—C16—H16B	109.4
C8—C7—C6	112.4 (3)	C17—C16—H16B	109.4
C8—C7—H7A	109.1	H16A—C16—H16B	108.0
C6—C7—H7A	109.1	N1—C15—C16	111.1 (2)
C8—C7—H7B	109.1	N1—C15—H15A	109.4
C6—C7—H7B	109.1	C16—C15—H15A	109.4
H7A—C7—H7B	107.8	N1—C15—H15B	109.4
C5—C10—C9	112.4 (3)	C16—C15—H15B	109.4
C5—C10—H10A	109.1	H15A—C15—H15B	108.0
C9—C10—H10A	109.1	C18—C17—C20	112.2 (3)
C5—C10—H10B	109.1	C18—C17—C16	108.8 (2)
C9—C10—H10B	109.1	C20—C17—C16	111.1 (2)
H10A—C10—H10B	107.9	C18—C17—H17	108.2
C14—C11—C13	110.2 (4)	C20—C17—H17	108.2
C14—C11—C6	114.0 (3)	C16—C17—H17	108.2
C13—C11—C6	112.4 (3)	C17—C20—H20A	109.5
C14—C11—H11	106.5	C17—C20—H20B	109.5
C13—C11—H11	106.5	H20A—C20—H20B	109.5
C6—C11—H11	106.5	C17—C20—H20C	109.5
C8—C9—C10	108.7 (3)	H20A—C20—H20C	109.5
C8—C9—C12	112.9 (4)	H20B—C20—H20C	109.5
C10—C9—C12	110.2 (3)	C3—N1—C15	123.8 (2)
C8—C9—H9	108.3	C3—N1—C19	123.74 (19)
C10—C9—H9	108.3	C15—N1—C19	112.4 (2)
C12—C9—H9	108.3	C4—O3—C5	115.85 (16)
C7—C8—C9	111.0 (3)	C1—O1—C4	109.6 (2)
C7—C8—H8A	109.4	C9—C12—H12A	109.5
C9—C8—H8A	109.4	C9—C12—H12B	109.5
C7—C8—H8B	109.4	H12A—C12—H12B	109.5
C9—C8—H8B	109.4	C9—C12—H12C	109.5
H8A—C8—H8B	108.0	H12A—C12—H12C	109.5
C11—C13—H13A	109.5	H12B—C12—H12C	109.5

D—H···A	D—H	H···A	D···A	D—H···A
C4—H4···O2i	0.98	2.44	3.376 (3)	160
C18—H18B···O2ii	0.97	2.54	3.393 (4)	147

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C4—H4⋯O2i	0.98	2.44	3.376 (3)	160
C18—H18B⋯O2ii	0.97	2.54	3.393 (4)	147

Symmetry codes: (i) ; (ii) .