Ammonia → HCID 68227446, compound

Participants

Reaction Steps

A solution of (R)-5-(5-bromo-2-fluorophenyl)-6,6-difluoro-5,7,7-trimethyl-1,4-oxazepane-3-thione (intermediate B7.1) (959 mg, 2.51 mmol) in methanol (27 ml) was treated consecutively with ammonia in methanol (7M; 21.5 ml, 151 mmol) and dropwise with tert-butylhydroperoxide (70% in water; 2.07 ml, 15.1 mmol). The reaction mixture was stirred at room temperature overnight. For the workup, the methanol was evaporated at reduced pressure, and the residue partitioned between dichloromethane and water. The organic layer was washed with brine, then the 2 aqueous layers extracted with dichloromethane. The combined organic layers were dried over sodium sulphate and evaporated at reduced pressure. The first purification of the crude product by chromatography on silica-amine phase using a gradient of heptane/ethyl acetate=100:0 to 72:28 was followed by a filtration through a SCX-2 cartridge. The cartridge was washed with a mixture of heptane and ethyl acetate and the product was recovered eluting with a solution of ammonia in methanol (7M). The (R)-5-(5-bromo-2-fluoro-phenyl)-6,6-difluoro-5,7,7-trimethyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-ylamine was obtained as a light yellow foam (463 mg, 51% yield). MS (ISP): m/z=365.2 [(M+H)+] and 367.1 [(M+2+H)+].

Provenance & Evidence