4-(5-Chloro-2-fluorobenzoyl)nicotinic acid → 4-(5-Chloro-2-fluorobenzyl)nicotinic acid

Participants

Reaction Conditions

Reaction Steps

Zinc-copper couple (0.75 g) is added to a stirred mixture of 4-(5-chloro-2-fluorobenzoyl)nicotinic acid and 3-(5-chloro-2-fluorobenzoyl)isonicotinic acid of Preparative Example 18 (94/6 on a molar base; 0.60 g) in 75% formic acid. The exothermic and effervescent reaction mixture is stirred for 15 min before heating to 80° C. for 2 hours. After cooling to 40° C., the mixture is filtered through a sintered glass funnel. The solid is washed with 75% formic acid (1×5 mL) and ethyl acetate (2×5 mL). The mixture is concentrated by roto-evaporation to about 2 mL. The orange oil obtained is dissolved in 0.5N HCl (3 mL) and extracted with ethyl acetate (3×10 mL), then saturated with NaCl and extracted with ethyl acetate/1,2-dimethoxyethane (2×5 mL). The combined extracts are dried with Na2SO4 and the solvents removed by roto-evaporation to yield a yellow foam. The foam (0.541 g) is recrystallized in hot acetonitrile (1 mL) to yield 4-(5-chloro-2-fluorobenzyl)nicotinic acid (0.142 g).

Provenance & Evidence