Diisopropyl Ether → N-Boc-sitagliptin

Participants

Reaction Steps

100 g of 3-tert-butoxycarbonylamino-4-(2,4,5-trifluorophenyl)butyric acid of formula (II) was charged with 800 ml of toluene into a 2 liter 4 necked round bottom flask attached with dean stark apparatus followed by 70 ml of triethyl amine at room temperature. Then 100 g of 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine HCl was charged and stirred for 5 minutes. 7.5 g of phenyl boronic acid was charged to the reaction mass. After 48 hours of stirring at reflux temperature, the reaction was complete. The reaction mass was cooled to room temperature and 1000 ml of water was added to it. The organic layer was separated and washed twice with 500 ml of 1N HCl. The organic layer was separated and washed with 500 ml of water followed by 6% NaHCO3 and finally by 500 ml of water. The organic layer was then separated, treated with sodium sulfate and then with charcoal and filtered. The solvent was distilled out under vacuum. The solid obtained was stirred with 500 ml of diisopropyl ether for 2 hours, filtered, washed with diisopropyl ether and then dried under vacuum at 50° C. for 12-15 hours.

Provenance & Evidence