tert-Butyl methyl ether → HCID 68647086, compound

Participants

Reaction Conditions

Reaction Steps

79.1 To a solution of 17.1 g (98.2% GC purity) of trans, rac-3-cyano-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (prepared according to C. Y. Hong et al. (Bioorganic Medicinal Chemistry Letters, 2003, 13, 4399), by D. J. Kim et al. (Journal of Medicinal Chemistry, 1997, 40, 3584) or by S. U. Hansen & M. Bols (Acta Chemica Scandinavica, 1997, 52, 1214)) in 765 ml of t-butylmethyl ether and 85 ml of vinyl acetate was added 21.3 g of Lipase AK (Amano Enzyme Inc.) and the suspension was stirred at 22° C. until ca. 54% conversion (as calculated from the ee-values of substrate and product according to C. J. Sih et al. (J. Am. Chem. Soc., 1982, 104, 7294)) was reached. The enzyme was filtered off, the filtrate evaporated in vacuo and the residual oil chromatographed on 400 g silicagel (0.040-0.063 mm; dichloromethane/diethyl ether 9:1→3:1) to give the formed optically enriched (S,S)-3-acetoxy-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester (10.7 g; 84% ee, optically further enriched in example 60.2) and the retained (R,R)-3-cyano-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (6.9 g). Analytics: +EI-MS: 213.3 (M+H+); [α]D=+1.20° (c=1.00, CHCl3); 97.8% ee (GC on BGB-176; 30 m×0.25 mm; H2; 90 kPa; 130° C. to 200° C. with 2° C./min; inj. 200° C.).

Provenance & Evidence