Ammonia → (R)-5-(5-Bromo-2-fluoro-phenyl)-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine

Participants

Reaction Steps

A pressure tube was charged with a solution of (R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-morpholine-3-thione (1.93 g, 6.3 mmol) in methanol (195 ml). A solution of ammonia in methanol (7M, 54 ml, 381 mmol) and an aqueous solution of tert-butyl hydroperoxide (70%, 8.17 g, 63.4 mmol) were added. The tube was sealed and the reaction mixture was stirred overnight at room temperature for 21 hours. For the workup, the reaction mixture was diluted with water and extracted three times with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulphate and evaporated. The crude product was purified by chromatography on an Isolute flash NH2 column using dichloromethane as the eluent. The (R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine was obtained as an off-white gum (1.42 g, 62% of theory). MS (ISP): m/z=287.1 [M+H]+, 289.0 [M+2+H]+.

Provenance & Evidence