Methyl iodide → 2-(3-Fluoro-4-(methylthio)phenyl)propanoic acid

Participants

Reaction Conditions

Reaction Steps

2-(3-Fluoro-4-(methylthio)phenyl)acetic acid (3 g, 0.01 mol) was dissolved in dry THF (60 mL) and the mixture was cooled to −78° C. Lithium bis(trimethylsilyl)amide (45 mL, 3 eq) was added at −78° C. and the mixture was stirred for 1 h at the same temperature. Methyl iodide (0.93 mL, 1 eq) was added at −78° C., the mixture was allowed to come to room temperature and stirred for 3 h at the same temperature. Progress of the reaction was monitored by TLC (50% ethyl acetate/hexane, Rf˜0.5). Although the reaction had not been completed the mixture was worked-up. The reaction contents were quenched with saturated ammonium chloride solution at 0° C. The contents were acidified with diluted HCl, the organic layer was separated and the aqueous layer was extracted with ethyl acetate (2×50 mL). the combined extract was dried over sodium sulfate, concentrated under reduced pressure and the crude product obtained was purified by column chromatography (10% ethyl acetate/hexane) to yield 2-(3-fluoro-4-(methylthio)phenyl)propanoic acid as an yellow solid (1 g, 31%).

Provenance & Evidence