HCID 11502325, compound → HCID 11595925, compound

Participants

Reaction Steps

A solution of [3-(4-chlorophenylsulfanyl)-2-methyl-4-nitro-1H-indol-1-yl]acetic acid, ethyl ester (1.99 kg, 4.92 mol) in ethyl acetate (24.2 kg) was hydrogenated in the presence of a 1% Pt/C catalyst paste (1.39 kg 44% w/w) under 4 bar A hydrogen pressure. After 2 hours hydrogen uptake had ceased so the reaction mixture was inerted then filtered through Celite (2.60 kg). The solids were washed with ethyl acetate (3×8 kg) and the combined filtrates distilled until a volume of 26 L remained to leave a solution of [4-amino-3-(4-chlorophenylsulfanyl)-2-methylindol-1-yl]acetic acid, ethyl ester in ethyl acetate. This solution was cooled to 4° C. then triethylamine (0.50 kg, 4.94 mol) added, followed by an ethyl acetate line wash (0.82 kg). A solution of acetyl chloride (0.39 kg, 4.97 mol) in ethyl acetate (3 kg) was added followed by an ethyl acetate line wash (0.76 kg). The reaction mixture was heated at 40° C. for 17 hours then water (16.9 kg) added. The reaction mixture was distilled down until 24.6 kg of distillate had been removed then cooled to 20° C. The solid product was collected by filtration, washed with water (1.9 kg) followed by acetonitrile (1.6 kg) then dried in a vacuum oven at 40° C. to afford [4-acetylamino-3-(4-chlorophenylsulfanyl)-2-methyl-1H-indol-1-yl]acetic acid, ethyl ester, 1.69 kg (82%) as an off white solid.

Provenance & Evidence