Methyl iodide → 2-Fluoro-5-methoxy-4-methylbenzoic acid

Participants

Reaction Conditions

Reaction Steps

Potassium tert-butoxide (7.92 g, 70.5 mmol) was dissolved in THF (150 mL) and cooled to −78° C. 2-Fluoro-5-methoxybenzoic acid (3.00 g, 17.6 mmol) in THF (100 mL) was added followed by n-butyl lithium (2.5 N in hexanes, 28.2 mL, 70.5 mmol). After 40 minutes, iodomethane (2.2 mL, 35.4 mmol) was added and allowed to stir at −78° C. for 70 minutes before warming to room temperature. The reaction was quenched with saturated ammonium chloride (100 mL) and extracted with ether. The aqueous layer was acidified using 6 N HCl then extracted with ether. The organic layer was dried over sodium sulfate, filtered and concentrated. The crude material was purified by Gilson reverse-phase HPLC (acidic mobile phase) to yield 2-fluoro-5-methoxy-4-methylbenzoic acid as a white solid. MS m/z=185 [M+1]+. Calc'd for C9H9FO3: 184.20.

Provenance & Evidence