tert-Butyl mercaptan → 3-[1-(4-Bromo-benzyl)-3-tert-butylsulfanyl-5-hydroxy-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

To a reaction vessel containing dichloromethane (3.3-fold, V/W of starting material) was added 3-[1-(4-bromo-benzyl)-3-tert-butylsulfanyl-5-methoxy-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester (1.0 eq) under nitrogen. 2-Methyl-2-propanethiol (7.80 eq) was added to the mixture, and the reaction was cooled to a temperature of −5-0° C. While maintaining the reaction mixture at less than 0° C., aluminum chloride (3.30 eq) was added portion-wise, and the reaction was stirred at 0-5° C. for 2 hours. Once no starting material was seen by tlc analysis (5% ethyl acetate/hexanes), the reaction was warmed to room temperature and quenched with ice-water (6.5-fold, V/W of starting material). The mixture was acidified to pH 2 with aqueous 2.0M hydrochloric acid, and the organic layer was separated. The aqueous layer was extracted with dichlormethane to recover remaining product, and the combined organic layers were washed successively with aqueous 1.0M hydrochloric acid, water, and brine, and concentrated in vacuo. Ethyl acetate (1.0-fold, V/W of starting material) was added to the crude material, and the mixture was heated until all the product was in solution. The flask was gradually cooled to 0-2° C., and hexane (11.0-fold, V/W of starting material) was slowly added. The mixture was agitated for 2 hours, and the precipitate was isolated by filtration and dried under vacuum to give the desired product.

Provenance & Evidence