Citric Acid → 5-(4-Chlorophenyl)-6-(cyclopropylmethoxy)nicotinic acid

Participants

Reaction Steps

6-Chloro-5-(4-chloro-phenyl)-nicotinic acid (22.3 g, 0.083 mol) was dissolved in dimethylsulfoxide (130 mL). To this solution was added (hydroxymethyl)cyclopropane (10.1 g, 0.125 mol) and potassium hydroxide powder (18.7 g, 0.333 mol). This mixture was reacted (in ten portions) for 20 min in a microwave at 100° C. The reaction mixture was poured into ice-water (500 mL) and citric acid (10%, 3000 mL) was added with stirring. Stirring was continued for 30 min during which time the product precipitated. The product was filtered off washed with water and dissolved in ethylacetate (1500 mL). The solution was concentrated in vacuo and the title compound crystallized from the concentrated solution as a white solid (21.5 g); MS (ISP) 302.2 (M−H)

Provenance & Evidence