Lithium hydroxide, monohydrate → AM-103 free acid

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence