Ammonia → Dimiracetam

Participants

Reaction Conditions

Reaction Steps

A suspension of 90.0 g (0.798 mol) of glycinamide hydrochloride (purity 98%) in 7.2 liter of n-propanol is heated to reflux, and 250 ml of solvent are distilled off. A 15% w/v solution of sodium tert-butoxide in n-propanol (260 ml, 0.35 mol) are added and an apparent pH of 5.5 is measured. Maintaining this apparent pH at 5.5 by automatic addition of a 15% w/v solution of sodium tert-butoxide in n-propanol, ethyl 4-oxobutanoate (purity 97%) (262.3 g, 1.955 mol) is added dropwise during four hours while keeping the reaction mixture at reflux, continuously distilling the solvent at about 400 ml/h and continuously adding n-propanol to the reaction mixture at about 400 ml/h. A total amount of 363 ml (0.476 mol) of sodium tert-butoxide 15% w/w solution in n-propanol is added. The mixture is stirred at reflux for additional 1.5 hours and then cooled to 65° C. A 7.5% w/w solution of ammonia in n-propanol (800 g) is slowly added to the mixture during 6 hours, and heating at 65° C. is continued for additional 18 hours. The reaction mixture is cooled to room temperature and the precipitate is filtered off. The clear solution is concentrated to a small volume (about 0.5 liter) under vacuum and stirred at 0° C. for 2 hours. The white precipitate is collected by suction filtration, washed with 50 ml of n-propanol and dried under vacuum at 60° C. for 12 hours to afford pure dimiracetam (65 g, 58.1%), melting at 154° C. HPLC purity: 99.7%

Provenance & Evidence