Acetonitrile → HCID 71008637, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of (1S,2S)-rel-2-((R)-1-amino-2,2-difluoro-3-hydroxy-1-methyl-propyl)-cyclopropane-carboxylic acid ethyl ester (542 mg, 2.28 mmol) and cyanogen bromide in acetonitrile (5M; 685 μl, 3.43 mmol) in ethanol (14 ml) was heated at 75° C. for 7 hours. In order to complete the reaction another volume of cyanogen bromide in acetonitrile (5M; 228 μl, 1.14 mmol, Eq: 0.50) was added and heating continued at 75° C. for 6 hours, and again cyanogen bromide in acetonitrile (228 μl, 1.14 mmol, Eq: 0.50) was added and heating continued at 75° C. for 24 hours. For the workup, the solution was evaporated, the residual oil was washed once with a solution of sodium carbonate (2M) and twice with ethyl acetate, then dried over sodium sulphate, filtered and concentrated at reduced pressure. The light yellow oil (731 mg) was purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 50:50 as the eluent. The (1S,2S)-rel-2-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-cyclopropanecarboxylic acid ethyl ester (404 mg, 67% yield) was obtained as a colorless oil. MS (ISP): m/z=263.2 [M+H]+.

Provenance & Evidence