Triethylamine → (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

Participants

Reaction Conditions

Reaction Steps

A solution of [(R)-1-(5-bromo-2-fluoro-phenyl)-2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-(4-methoxy-benzyl)-amine (1.035 g, 2.15 mmol) in acetonitrile (16 ml) was treated with triethylamine (0.36 ml, 2.57 mmol). The mixture was cooled to 10° C. and a solution of (RS)-2-chloro-2-phenyl-acetyl chloride (0.34 ml, 2.36 mmol) in acetonitrile (2 ml) was added slowly. The reaction mixture was allowed to warm to room temperature and was stirred for 3 hours. Because the transformation was not complete, triethylamine (0.33 ml, 2.36 mmol) was again added, the reaction mixture cooled to −5° C., then treated with a solution of (RS)-2-chloro-2-phenyl-acetyl chloride (0.31 ml, 2.15 mmol) in acetonitrile (1 ml). The reaction mixture was allowed to warm to room temperature and was stirred for 22 hours. Thereafter, the mixture was evaporated at reduced pressure and without further workup directly purified by chromatography on Silicycle-Si-amine column using a gradient of heptane and ethyl acetate=100/0 to 70/30 as the eluent. (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 was obtained as a white foam (1.068 g, 78% of theory). Mass (calculated) C31H38BrClFNO3 [635.09]; (found) [M+H]+=638, [M+2-H]+=636, [M+4-H]+=634.

Provenance & Evidence