Diisopropyl Ether → N-Boc-sitagliptin

참여 물질

반응 단계

25 g of 3-tert-butoxycarbonylamino-4-(2,4,5-trifluorophenyl)butyric acid of formula (II) was charged with 200 ml of toluene into a 500 ml 4 necked round bottom flask attached with dean stark apparatus, followed by the addition of 25 ml of Hunig's base at room temperature. Then 25 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. 11.5 g of 2-chloro 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 250 ml of water was added to it. The organic layer was separated and washed twice with 125 ml of 1N HCl. The organic layer was separated and washed with 125 ml of water followed by 6% NaHCO3 and finally by 125 ml of water. The organic layer was then separated and the solvent was distilled out under vacuum. The solid obtained was stirred with 125 ml of diisopropyl ether for 2 hours, filtered and then dried under vacuum at 50° C. for 12-15 hours. HPLC was used to obtain the chromatographic purity and chiral purity.

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