反应详情

温度

5 °C

(2R)-4-oxo-N-[(1R)-1-phenylethyl]-1-(2,4,5-trifluorophenyl)-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]butan-2-amine [F] (25 g, 0.049 mol) was subjected to hydrogenolysis in methanol (75 ml) containing acetic acid (3.0 ml, 0.052 mol) using 5% palladium on charcoal as catalyst at 52±2° C. at hydrogen pressure of 2.0±0.5 kg/cm2. After completion on reaction the catalyst was removed by filtration and reaction mass was concentrated under vacuum. Obtained residue was suspended in water and pH was set to 10.0±0.4 with solution of potassium carbonate. Product was extracted into dichloromethane. The extract was concentrated and degassed. The obtained syrupy mass was dissolved in ethanol, phosphoric acid (3.5 ml, 0.060 mol) was added and the solution refluxed for 30 min. Cooled to 5±3° C., filtered the solid and dried to obtain 20.9 g sitagliptin phosphate, chromatographic purity was 99.8%; chiral purity (determined by chiral HPLC) was 100%.

1. customat 52±2° C.
2. customAfter completion on reaction the catalyst
3. customwas removed by filtration and reaction mass
4. concentrationwas concentrated under vacuum
5. extractionProduct was extracted into dichloromethane
6. concentrationThe extract was concentrated
7. customdegassed
8. dissolutionThe obtained syrupy mass was dissolved in ethanol
9. temperaturethe solution refluxed for 30 min
10. filtrationfiltered the solid
11. customdried