Hydrochloric Acid → 4-(Adamantan-1-ylmethoxy)-2-fluoro-5-(trans-2-methylcyclopropyl)benzoic acid

Participants

Reaction Conditions

Reaction Steps

To a mixture of diethylzinc (1.0 M solution in heptane, 6.75 mL, 6.75 mmol) in anhydrous dichloromethane (2 mL) was added a solution of trifluoroacetic acid (0.52 mL, 6.80 mmol) in anhydrous dichloromethane (3 mL) at 0° C. and the reaction mixture was stirred for 10 minutes at 0° C. A solution of diiodomethane (0.54 mL, 6.75 mmol) in dichloromethane (2 mL) was added to the reaction mixture at 0° C. and stirring was continued for 10 minutes at 0° C. To the reaction mixture was then added a solution of tert-butyl 4-(adamantan-1-ylmethoxy)-2-fluoro-5-((E)-prop-1-en-1-yl)benzoate (0.90 g, 2.25 mmol) in anhydrous dichloromethane (3 mL) at 0° C. The reaction mixture was allowed to warm to ambient temperature and stirred for 4 hours. After addition of 1 N hydrochloric acid (10 mL), the mixture was diluted with dichloromethane (100 mL). The organic phase was dried over anhydrous sodium sulfate and filtered. Concentration of the filtrate gave a residue which was purified by reverse-phase preparative HPLC to afford the title compound as an off-white solid (0.086 g, 11%): MS (ES−) m/z 357.3 (M−1).

Provenance & Evidence