Phosphoric Acid → (S)-Sitagliptin Phosphate

Participants

Reaction Conditions

Reaction Steps

In a 25 mL round bottom flask isopropanol (4.0 mL) was taken. Then (2R:2S, 70:30)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (2.0 g) was added. The reaction mixture was heated at 70-75° C. Subsequently 85% Phosphoric acid (481 mg, 0.33 mL) was added over a period of 15-20 mins. Solid mass was precipitated out during addition. After a solvent mixture of water (1.8 mL) and IPA (14.0 mL) was added into the reaction mixture, keeping the temperature between 68-70° C. The slurry was aged for 2-3 h at 68-70° C. Then the slurry was cooled to room temperature. Solid mass was filtered off and washed with cold IPA. Solid mass was dried and collected. Wt. of titled compound-1.8 g. % Purity by HPLC-99.7%, % chiral purity by HPLC of R-isomer 72.8%.

Provenance & Evidence