Ethyl oxoacetate → (RS)-[4-(tert-butyl-diphenyl-silanyloxy)-2,6-difluoro-phenyl]-hydroxy-acetic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

A well stirred solution under N2 of tert-butyl-(3,5-difluoro-phenoxy)-diphenyl-silane (20.0 g) and N,N,N′,N′-pentamethyldiethylenetriamine (9.9 g) in dry THF (600 ml) was cooled to −75° C. A 1.6 M sol. of BuLi in Hex (35.6 ml) was added via syringe. The reaction mixture was stirred 1 h under cooling (−78° C.). A white precipitate was formed. Glyoxalic acid ethyl ester (50% in Tol, 22.2 g) was added and it was stirred 2 h at −78° C. The cooling bath was removed and the clear solution was left to warm to −10° C. (1 h). After dilution with TBME (500 ml) the mixture was washed with 1 N HCl (2×500 ml) and brine (250 ml), dried over MgSO4 and the solvent was evaporated. The crude product was purified by CC (Hept, then Hept/CH2Cl2 1:4). 27.9 g (60%) of (RS)-[4-(tert-butyl-diphenyl-silanyloxy)-2,6-difluoro-phenyl]-hydroxy-acetic acid ethyl ester were obtained next to 7.3 g (36%) of recovered starting material. Colorless viscous oil. MS 488.4 ([M+NH4]+).

Provenance & Evidence