反应详情

温度

55 °C

3-[5-(Pyrid-2-ylmethoxy)-3-(2-methyl-2-propylthio)-1-[4-(2-methoxypyrid-5-yl)benzyl]indol-2-yl]-2,2-dimethylpropionic acid ethyl ester (693 g, 1.086 mol) was added to a reactor containing 6.91 L of THF/MeOH/water in a 2:1:1 ratio and stirred. LiOH.H2O (54.75 g, 1.3 mol) was added to the reactor and the mixture was heated to between 50 to 60° C. and stirred overnight (about 12 hours). TLC analysis (EtOAc/Petroleum ether, 1/5) showed the reaction had reached completion. The THF/MeOH/water solvent mixture was removed in vacuo and about 6 liters of water was added. The organic impurities were removed with extraction using EtOAc in 1.5 liter batches. The pH of the aqueous layer was adjusted to a pH of between 2 and 3 using 3N HCl. The compound was extracted twice with dichloromethane in 6 liter batches. Following a water wash and a brine wash, the organic layer was dried over Na2SO4. The solid was filtered and the organic layer was concentrated in vacuo to afford 623 g of desired product in 94% yield.

1. stirringstirred overnight (about 12 hours)
2. customThe THF/MeOH/water solvent mixture was removed in vacuo and about 6 liters of water
3. additionwas added
4. customThe organic impurities were removed with extraction
5. extractionThe compound was extracted twice with dichloromethane in 6 liter batches
6. washwash
7. washa brine wash
8. dry with materialthe organic layer was dried over Na2SO4
9. filtrationThe solid was filtered
10. concentrationthe organic layer was concentrated in vacuo