Acetic Acid → (2,3-Difluoro-6-nitrophenyl)acetic acid

Participants

Reaction Steps

64 g of 60% sodium hydride was added to 200 ml of tetrahydrofuran, and, while the mixed solution was stirred and cooled on ice, a solution obtained by dissolving 258 g of diethyl malonate in 400 ml of tetrahydrofuran was dropped to the mixed solution through 1 hour and 40 minutes so that the reaction temperature was kept below 20° C. Then, while the reaction solution was stirred and cooled on ice, 200 ml of tetrahydrofuran solution dissolving 142 g of 2,3,4-trifluoronitrobenzene was dropped to the reaction solution through 2 hours so that the reaction temperature was kept below 10° C. After reacting at room temperature for 2 hours, 100 ml of acetic acid was added to the reaction solution and tetrahydrofuran was removed by distillation. To the residue, 1 l of chloroform, 1.5 l of water and 100 ml of concentrated hydrochloric acid were added, and the solution was separated. The organic layer was separated from the solution, and the solvent was removed by distillation. To the residue, 250 ml of 4N hydrochloric acid and 200 ml of acetic acid were added, and the solution was heated under reflux for 11 hours. After removing 150 ml of content solution by distillation, 50 ml of acetic acid and 50 ml of water were added to the solution, and the solution was heated under reflux for 31 hours. After the solution was air-cooled, the precipitated crystal was filtered off, washed with diisopropyl ether and was dissolved in 400 ml of methanol. After treating with active carbon, the solvent was removed by distillation. The precipitated crystal was dispersed in diisopropyl ether and was filtered off to obtain 100 g of the subject compound (1) in a 56% yield.

Provenance & Evidence