Ammonium Chloride → 4-(2-Fluoro-3-methoxyphenyl)-2-hydroxy-4-methylpentanoic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

19.58 g (77 mmol) of 4-(2-fluoro-3-methoxyphenyl)-4-methylpentanoic acid methyl ester is introduced into 245 ml of tetrahydrofuran, and the reaction mixture is cooled to −70° C. Within one hour, 220.7 ml of a 0.5 molar solution of potassium-bis-(trimethylsilylamide) in toluene is added in drops, and the reaction mixture is then stirred for 45 more minutes at −70° C. 28.3 g (107.79 mmol) of Davis reagent, dissolved in 245 ml of tetrahydrofuran, is now added in drops within 40 minutes. After two hours of stirring at −70° C., 250 ml of saturated ammonium chloride solution is slowly added in drops, and in this case, the batch is brought to room temperature. After extraction with methyl tert-butyl ether, the combined organic extracts are treated as usual with water and brine. After the solvent is spun off, the residue is chromatographed several times on silica gel (mobile solvent ethyl acetate/hexane). 12.14 g (58.3%) of the desired compound is ultimately isolated.

Provenance & Evidence