4-Methylmorpholine → (E)-2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-2'-isobutyl-4-methylvalerohydrazide

Participants

Reaction Conditions

Reaction Steps

A solution of 4.05 kg of (E)-2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-4-methylvaleric acid in 12 l of dimethylformanide was cooled to 4° C., treated with 1.97 kg of hydroxybenzotriazole hydrate and 2.466 kg of 1-ethyl-3-(3-dimethylaminopropyl)carbodimide hydrochloride and stirred for 2 hours at 4° C. 3.895 kg of isobutylhydrazine ditosylate salt were added followed by 2.36 l of N-methyl-morpholine. The mixture was stirred for 2 hours at 4° C. and for 50 hours at room temperature, diluted with 12 l of 2M hydrochloric acid and 12 l of methyl tert.butyl ether and the organic layer was separated. The organic phase was washed with water, saturated sodium hydrogen carbonate solution and water and then evaporated to give a dark cream colored solid. Recrystallization from hexane gave 2.47 kg of (E)-2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-2′-isobutyl-4-methylvalerohydrazide in the form of a cream colored solid.

Provenance & Evidence