(5S)-3-Chloro-5-[(1R,2S,5R)-2-isopropyl-5-methyl­cyclo­hex­yloxy]-4-(4-methyl­piperidin-1-yl)furan-2(5H)-one

Xiao-Mei Wang; Jian-Hua Fu; Song-Liang Cai; Zhao-Yang Wang

doi:10.1107/S1600536811005216

. 2011 Feb 19;67(Pt 3):o656. doi: 10.1107/S1600536811005216

(5S)-3-Chloro-5-[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy]-4-(4-methylpiperidin-1-yl)furan-2(5H)-one

Xiao-Mei Wang ^a, Jian-Hua Fu ^a, Song-Liang Cai ^a, Zhao-Yang Wang ^a,^*

PMCID: PMC3051989 PMID: 21522408

Abstract

The title compound, C₂₀H₃₂ClNO₃, was obtained via a tandem asymmetric Michael addition–elimination reaction of (5S)-3,4-dichloro-5-(l-menthyloxy)furan-2(5H)-one and 4-methylpiperidine in the presence of potassium fluoride. The furanone ring is approximately planar [maximum atomic deviation = 0.022 (2) Å] while the cyclohexane ring adopts a chair conformation. Weak intermolecular 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 _r = 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
Δρ_max = 0.13 e Å⁻³
Δρ_min = −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.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811005216/go2003sup1.cif

e-67-0o656-sup1.cif^{(21KB, cif)}

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

e-67-0o656-Isup2.hkl^{(220.7KB, hkl)}

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

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

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

The work was supported by the National Natural Science Foundation of China (grant No. 20772035) and the Natural Science Foundation of Guangdong Province, China (grant No. 5300082).

supplementary crystallographic information

Comment

2(5H)-furanones are heterocyclic carbonyl compounds, which are widespread in natural and in synthetic products (Prasad & Gandi, 2010; Steenackers et al., 2010). 5-menthyloxy-3,4-dihalo-2(5H)-furanones, being a kind of chiral synthons, are widely used in asymmetric Michael addition-elimination tandem reactions (Song et al., 2009). 4-amino-2(5H)-furanones show an antibiotic activity against Staphylococcus aureus (Lattmann et al., 2005).

We are interested in the tandem Michael addition-elimination reaction of the chiral synthon 3,4-dichloro-5-(S)-(l-menthyloxy)-2(5H)-furanone and 4-methylpiperidine in the presence of potassium fluoride. The structure of the title compound (I) is illustrated in Fig. 1. The crystal structure of the title compound, which has four chiral centers (C4(S), C5(R), C6(S), C9(R)) contains a five-membered furanone ring and a six-membered cyclohexane ring connected each other via C4—O3—C5 ether bond. The furanone ring of C4—O1—C1—C2—C3 is approximately planar, whereas a six-membered cyclohexane ring displays a chair conformation. At the same time, the furanone ring is connected to piperidine heterocycle via C3—N1 bond.

Experimental

The precursor 3,4-dichloro-5-(S)-(l-menthyloxy)-2(5H)-furanone was prepared according to the literature procedure (Song et al., 2009). After the mixture of 3,4-dichloro-5-(S)-(l-menthyloxy)-2(5H)-furanone (2.0 mmol) and potassium fluoride (6.0 mmol) was dissolved in absolute tetrahydrofuran (2.0 mL) under nitrogen atmosphere, tetrahydrofuran solution of 4-methylpiperidine (2.0 mmol) was added. The reaction was carried out by stirring at room temperature for 24 h. Once the reaction was complete, the solvents were removed under reduced pressure. The residual solid was dissolved in dichloromethane. Then the combined organic layers from extraction were concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography with the gradient mixture of petroleum ether and ethyl acetate to give the product yielding (I) 0.5685 g (76.8%).