反应详情

A solution of (R)-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino) butanoic acid (INTERMEDIATE 8, 1.99 g, 4.01 mmol) and HATU (1.83 g, 4.82 mmol) in DMA (18.0 ml) was treated with morpholine (0.35 ml, 4.02 mmol) and DIPEA (1.40 ml, 8.02 mmol). The resulting reaction mixture was stirred at room temperature for 1 hour and then diluted with EtOAc (250 ml). The organic layer was washed with water (3×250 ml), 1M aq. NaHSO4 (200 ml), and saturated aq. NaHCO3 (200 ml). The organic layer was dried (Na2SO4), filtered, and evaporated under reduced pressure to provide a sticky foam. The foam was dissolved in EtOAc (40 ml) and washed with water (2×250 ml). During the second wash material precipitated. EtOAc (80 ml) was added and the resulting mixture was shaken, resulting in redissolution of the precipitate. The mixture was further dried (Na2SO4), filtered, and evaporated under reduced pressure. The residue was dissolved in a few ml of DCM resulting in the formation of a precipitate. Finally, evaporation of the volatiles under reduced pressure afforded the title product (2.02 g, yield: 89%).

1. customThe resulting reaction mixture
2. washThe organic layer was washed with water (3×250 ml), 1M aq. NaHSO4 (200 ml), and saturated aq. NaHCO3 (200 ml)
3. dry with materialThe organic layer was dried (Na2SO4)
4. filtrationfiltered
5. customevaporated under reduced pressure
6. customto provide a sticky foam
7. washwashed with water (2×250 ml)
8. customDuring the second wash material precipitated
9. additionEtOAc (80 ml) was added
10. stirringthe resulting mixture was shaken
11. customresulting in redissolution of the precipitate
12. dry with materialThe mixture was further dried (Na2SO4)
13. filtrationfiltered
14. customevaporated under reduced pressure
15. dissolutionThe residue was dissolved in a few ml of DCM resulting in the formation of a precipitate
16. customFinally, evaporation of the volatiles under reduced pressure