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

Jian-Hua Fu; Zhao-Yang Wang; Kai Yang; Chao-Xu Mao

doi:10.1107/S1600536810026929

. 2010 Jul 14;66(Pt 8):o2022. doi: 10.1107/S1600536810026929

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

Jian-Hua Fu ^a, Zhao-Yang Wang ^a,^*, Kai Yang ^a, Chao-Xu Mao ^a

PMCID: PMC3007345 PMID: 21588333

Abstract

The title compound, C₂₀H₃₃ClN₂O₃, was obtained via a tandem asymmetric Michael addition–elimination reaction of 3,4-dichloro-5-(S)-(l-menthyloxy)furan-2(5H)-one and 1-ethylpiperazine in the presence of potassium fluoride. The molecular structure contains an approximately planar five-membered furanone ring [maximum atomic deviation = 0.024 (2) Å] and two six-membered rings adopting chair conformations. Weak intermolecular 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 _r = 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
Δρ_max = 0.13 e Å⁻³
Δρ_min = −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.

Supplementary Material

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

e-66-o2022-sup1.cif^{(21.3KB, cif)}

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

e-66-o2022-Isup2.hkl^{(214.8KB, 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	2.53	3.361 (4)	142

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Symmetry code: (i) Inline graphic .

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

With their poly-functional groups and highly active reactivity, 5-menthyloxy-2(5H)-furanones, serving as a kind of important building blocks, were widely used for the synthesis of a variety of chiral 5-menthyloxy-2(5H)-furanone derivatives. Until now, the asymmetric Michael addition reactions of 2(5H)-furanone with nucleophiles, to construct C-X (X=N, O, S, P, C) bond, have been a prominent objective in furanone chemistry (Bertrand et al., 2000; He et al., 2006; Sarma et al., 2007). At the same time, 4-amino-2(5H)-furanone is an attractive moiety in chemical, pharmaceutical and agrochemical research (Kimura et al., 2000; Tanoury et al., 2008).

Therefore 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 1-ethylpiperazine in the present 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 two six-membered rings connected each other via C4—O3—C5 ether bond and C3—N2 bond. The furanone ring of C2—C3—C4—O1—C1 is approximately planar, whereas the six-membered ring displays a chair conformation.

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 1-ethylpiperazine (3.0 mmol) was added. The reaction was carried out under the 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) 0.280 g (36.1%).