Tetrabutylammonium Fluoride → (R)-3-(5-bromo-2-fluoro-phenyl)-4-(4-methoxy-benzyl)-3-methyl-[1,4]oxazepan-5-one

Participants

Reaction Conditions

Reaction Steps

N-[(R)-1-(5-Bromo-2-fluoro-phenyl)-2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-3-chloro-N-(4-methoxy-benzyl)-propionamide (2.08 g, 3.63 mmol) was dissolved in tetrahydrofurane (45 ml) and the solution cooled to 0° C. A solution of tetrabutylammonium fluoride (1 N in tetrahydrofuran, 7.25 ml) was added and the reaction mixture left to warm to room temperature. After 16 hours, the solvent was evaporated at reduced pressure, the residue dissolved in ethyl acetate (25 ml) and water (25 ml) and the mixture stirred for 15 minutes at room temperature. The aqueous layer was separated and extracted with ethyl acetate (50 ml). The organic layers were washed with brine (25 ml), combined, dried over sodium sulfate and evaporated at reduced pressure. After chromatography on Silicycle-Si-amine column using a gradient of heptane and ethyl acetate=100/0 to 20/10 as the eluent, (R)-3-(5-bromo-2-fluoro-phenyl)-4-(4-methoxy-benzyl)-3-methyl-[1,4]oxazepan-5-one (intermediate C10A) was obtained as a white foam (1.34 g, 88% of theory). MS (ISP): m/z=422.1, 424.2 [M+H]+.

Provenance & Evidence