Hydrochloric Acid → 6-(3-Fluoro-4-methylphenyl)-2-[(2-methylcyclopropyl)methoxy]-4-(trifluoromethyl)nicotinic acid

Participants

Reaction Steps

37 mg (0.431 mmol) of (2-methylcyclopropyl)methanol and 17 mg (0.431 mmol) of sodium hydride (60% strength dispersion in mineral oil) were initially charged in 5 ml of tetrahydrofuran. The reaction mixture was stirred at room temperature for 60 minutes. 100 mg (0.288 mol) of methyl 2-chloro-6-(3-fluoro-4-methylphenyl)-4-(trifluoromethyl)nicotinate (Example 2A) in 2 ml of tetrahydrofuran were then added. The mixture was stirred at reflux temperature for 3 h and then at room temperature overnight. For work-up, the reaction mixture was adjusted to pH 1 using 1N hydrochloric acid. After removal of the volatile components on a rotary evaporator, the product was purified by preparative HPLC (mobile phase: acetonitrile/water, gradient 10:90→90:10). This gave 20 mg (18% of theory) of the target compound.

Provenance & Evidence