(3R,4S)-1-(4-Meth­oxy­phen­yl)-2-oxo-4-(3-vinyl­phen­yl)azetidin-3-yl acetate

Xiao-Dong Hao; Cheng Xie; Yun-Peng Hao; Jun Chang; Xun Sun

doi:10.1107/S1600536813007897

. 2013 Mar 28;69(Pt 4):o601. doi: 10.1107/S1600536813007897

(3R,4S)-1-(4-Methoxyphenyl)-2-oxo-4-(3-vinylphenyl)azetidin-3-yl acetate

Xiao-Dong Hao ^a, Cheng Xie ^a, Yun-Peng Hao ^a, Jun Chang ^a, Xun Sun ^a,^*

PMCID: PMC3629641 PMID: 23634128

Abstract

In the title compound, C₂₀H₁₉NO₄, the absolute configuration (3R,4S) for the two chiral centres of the molecule has been determined.

Related literature

For the preparation of the title compound, an intermediate in the synthesis of C-4 to C-3′ bridged paclitaxel analogues, see: Ganesh et al. (2007 ▶).

Experimental

Crystal data

C₂₀H₁₉NO₄
M _r = 337.36
Monoclinic,
a = 20.7448 (4) Å
b = 6.3930 (1) Å
c = 15.7434 (3) Å
β = 124.309 (1)°
V = 1724.64 (5) Å³
Z = 4
Cu Kα radiation
μ = 0.74 mm⁻¹
T = 124 K
0.20 × 0.18 × 0.11 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2010 ▶) T _min = 0.866, T _max = 0.923
6072 measured reflections
2374 independent reflections
2330 reflections with I > 2σ(I)
R _int = 0.024

Refinement

R[F ² > 2σ(F ²)] = 0.026
wR(F ²) = 0.069
S = 1.06
2374 reflections
228 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.15 e Å⁻³
Absolute structure: Flack (1983 ▶), 730 Friedel pairs
Flack parameter: 0.01 (15)

Data collection: APEX2 (Bruker, 2010 ▶); cell refinement: SAINT (Bruker, 2010 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Click here for additional data file.^{(19.8KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536813007897/mw2104sup1.cif

e-69-0o601-sup1.cif^{(19.8KB, cif)}

Click here for additional data file.^{(2.9KB, cdx)}

Supplementary material file. DOI: 10.1107/S1600536813007897/mw2104Isup2.cdx

Click here for additional data file.^{(116.7KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813007897/mw2104Isup3.hkl

e-69-0o601-Isup3.hkl^{(116.7KB, hkl)}

Click here for additional data file.^{(5.8KB, cdx)}

Supplementary material file. DOI: 10.1107/S1600536813007897/mw2104Isup4.cdx

Click here for additional data file.^{(6.8KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813007897/mw2104Isup5.cml

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

Acknowledgments

The work was supported financially by the National Natural Science Foundation of China (No. 81172920), the Shanghai Municipal Committee of Science and Technology (No. 10431903100) and the National Basic Research Program of China (973 Program, No. 2010CB912603). We would like to thank Dr Jie Sun for the single-crystal X-ray determination.

supplementary crystallographic information

Comment

In our research on the conformation of a novel fluorinated, tubulin-bound, docetaxel analogue, one of the key intermediate products, the title compound (3R,4S)-1-(4-methoxyphenyl)-2-oxo-4-(3-vinylphenyl)azetidin-3-yl acetate C₂₀H₁₉NO₄ (I) (Fig. 1) was separated from the racemic 1-(4-methoxyphenyl)-2-oxo-4-(3-vinylphenyl)azetidin-3-yl acetate (Ganesh et al., 2007). The reaction scheme is shown in Fig. 2. The absolute configuration (3R,4S) for the two chiral centres of the molecule has been determined.

Experimental

Lipase PS (Amano) (2.25 g) was added to a solution of racemic 1-(4-methoxyphenyl)-2-oxo-4-(3-vinylphenyl)azetidin-3-yl acetate (2.26 g, 6.7 mmol) in 60 mL of CH₃CN and pH 7.0 phosphate buffer (1:9), and the resulting solution was stirred at r.t. for 120 h. The reaction mixture was filtered and extracted with EtOAc (200 mL × 2), the organic layers were combined and solvent was removed under reduced pressure. The residue was purified by flash column chromatography using petroleum ether/EtOAc (4/1) to furnish the title compound (3R,4S)-1-(4-Methoxyphenyl)-2-oxo-4-(3-vinylphenyl)azetidin-3-yl acetate (1 g, 49%) as a white solid. Suitable crystals were obtained by recrystallization from hexane and DCM (m.p. 391.8–392.9 K). ¹H NMR (400 MHz, CDCl₃): δ 1.71 (s, 3H), 3.88 (s, 3H), 5.28 (d, 1H, J = 10.96 Hz), 5.35 (d, 1H, J = 4.69 Hz), 5.75 (d, 1H, J = 17.61 Hz), 5.95 (d, 1H, J = 4.70 Hz), 6.62–6.76 (m, 1H), 6.81 (d, 2H, J = 9 Hz), 7.18–7.42 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 19.85, 55.45, 61.42, 76.32, 114.45, 114.80, 118.82, 125.86, 126.46, 127.28, 128.72, 130.31, 132.73, 136.20, 137.88, 156.66, 161.32, 169.24; ESIMS m/z 338.0 [M + H]⁺.