Tetrabutylammonium Fluoride → (2RS,5R)-5-(5-bromo-2-fluoro-phenyl)-4-(4-methoxy-benzyl)-5-methyl-2-phenyl-morpholin-3-one

Participants

Reaction Conditions

Reaction Steps

A solution of (RS)-N-[(R)-1-(5-bromo-2-fluoro-phenyl)-2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-2-chloro-N-(4-methoxy-benzyl)-2-phenyl-acetamide (1.068 g, 1.68 mmol) in tetrahydrofuran (30 ml) was cooled to 0° C. and treated dropwise during 10 minutes with a solution of tetrabutylammonium fluoride (1 M, 3.36 mmol) in tetrahydrofuran. The orange-colored reaction mixture was stirred at 0° C. for 5 minutes, then for 4 hours at room temperature. For the workup, the reaction mixture was evaporated at reduced pressure, the residue partitioned between water (10 ml) and ethyl acetate (25 ml) and stirred for 15 minutes. The layers were separated and the aqueous layer re-extracted with ethyl acetate (25 ml). The combined organic layers were dried over sodium sulfate and evaporated at reduced pressure. After chromatography on a Silicycle-Si-amine column using a gradient of heptane and ethyl acetate=100/0 to 50/50 as the eluent, the (2RS,5R)-5-(5-bromo-2-fluoro-phenyl)-4-(4-methoxy-benzyl)-5-methyl-2-phenyl-morpholin-3-one was obtained as a white foam (369 mg, 45% of theory). Mass (calculated) C25H23BrFNO3 [484.37]; (found) [M+H]+=484, [M+2-H]+=486.

Provenance & Evidence