Tetrahydrofuran → Diisopropylethylamine

Participants

Reaction Steps

A solution of allyl (4R,5R,6S)-4-(2"-azidoethyl)-6-[(1'R)-1'-tert-butyldimethylsilyloxyethyl]-3,7-dioxo-1-azabicyclo[3.2.0heptane-2-carboxylate (6.46 mmol, prepared by cyclization of 3.0 g, 6.46 mmol of the diazo precursor prepared in Example 2, Step E) in dry acetonitrile (50 mL) was treated at -15° C. and under Argon with diphenyl chlorophosphate (1.4 mL, 6.75 mmol) and N,N-diisopropylethylamine (1.2 mL, 6.9 mmol) added simultaneously over 5 min. A small crystal of 4-N,N-dimethylaminopyridine was then added and the temperature of the mixture was slowly warmed to 0°-5° C. over 30 min. N,N-Diisopropylethylamine (1.2 mL, 6.9 mmol) and 4-mercaptobutyronitrile (1.31 g, 13.0 mmol) [obtained from basic hydrolysis of an aqueous tetrahydrofuran solution of 4-acetylmercaptobutyronitrile (U.S. Pat. No. 3,223,585)] were added and the mixture was stirred at 0°-5° C. for 4 h and overnight at -15° C. The reaction mixture was then diluted with EtOAc (300 mL), washed with water, 1M NaHSO3, saturated NaHCO3, brine and dried (MgSO4). Evaporation of the solvent gave an oil which was chromatographed on silica gel (5×15 cm). Elution with a mixture of EtOAc and toluene (1:9) gave 2.62 g (78%) of the title compound as a brown oil:

Provenance & Evidence