反应详情

tert-Butyldimethylsilyl chloride (471 mg, 3.12 mmol) and imidazole (483 mg, 7.10 mmol) were added successively to a stirred solution of benzyl [(1S)-2-cyano-2-hydroxy-1-methylethyl]carbamate (665 mg, 2.84 mmol) in dry CH2Cl2 (13 mL) at room temperature under N2 and the mixture was stirred overnight. Water (30 mL) was added and the mixture was extracted with Et2O (3×30 mL). The combined extracts were dried (MgSO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 40×160 mm, 0-15% EtOAc in hexanes gradient) to afford benzyl ((1S,2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-cyano-1-methylethyl)carbamate and benzyl ((1S,2S)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-cyano-1-methylethyl)carbamate. (1S,2R)-diastereoisomer: Rf=0.29 (10% EtOAc in hexanes). LCMS calc.=349.2; found=349.1 (M+1)+. 1H NMR (500 MHz, CDCl3) δ 7.39-7.33 (m, 5H), 5.16 (d, J=12.1 Hz, 1H), 5.07 (d, J=12.1 Hz, 1H), 4.89 (br d, J=6.6 Hz, 1H), 4.68 (br, d, 3.6 Hz, 1H), 3.92 (m, 1H), 1.31 (d, J=6.7 Hz, 3H), 0.91 (s, 9H), 0.21 (s, 3H), 0.17 (s, 3H). (1S,2S)-diastereoisomer: Rf=0.24 (10% EtOAc in hexanes). LCMS calc.=349.2; found=349.1 (M+1)+. 1H NMR (500 MHz, CDCl3) δ 7.38-7.32 (m, 5H), 5.10 (s, 2H), 4.76 (br d, J=6.9 Hz, 1H), 4.63 (br s, 1H), 4.00 (m, 1H), 1.31 (d, J=6.8 Hz, 3H), 0.90 (d, J=2.9 Hz, 9H), 0.17 (s, 3H), 0.08 (s, 3H).

1. extractionthe mixture was extracted with Et2O (3×30 mL)
2. dry with materialThe combined extracts were dried (MgSO4)
3. concentrationconcentrated in vacuo
4. customto give the crude product
5. customThis was purified by flash chromatography (Si, 40×160 mm, 0-15% EtOAc in hexanes gradient)