Diazepam → Ethyl 5-chloro-3-phenyl-2H-isoindole-1-carboxylate

Participants

Reaction Steps

A solution of 28.5 g. of 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one in 400 ml. of dimethylformamide is treated under an atmosphere of argon at -10° C. with 0.25 mol. of sodium hydride (11.0 g. of a 55% dispersion in mineral oil) and the mixture is stirred at the same temperature for 15 minutes. The suspension is then treated at -10° C. to -5° C. with a solution of 35.5 g. of diethylcarbonate in 50 ml. of dimethylformamide. The mixture is stirred at 20° C. for 1 hour and at 60° C. for an additional 4 hours. Then, the mixture is poured on to a mixture of 100 g. of sodium chloride and 2.5 kg. of ice. The precipitate is removed by filtration, washed with water and dissolved in methylene chloride. The organic solution is washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated to dryness. The crystalline residue is heated to reflux with 500 ml. of ethanol for 10 minutes and then cooled in an ice-bath. After filtration and washing with ethanol and diethyl ether, there is obtained 5-chloro-3-phenylisoindole-1-carboxylic acid ethyl ester in the form of greenish crystals having a melting point of 208°-210° C. (decomposition). Recrystallization from acetonitrile does not increase the melting point.

Provenance & Evidence