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 CH2Cl2 (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). 2-Methyl-2-propanethiol (7.80 eq) was subsequently added to the reaction mixture and the reaction was cooled down to a temperature of −5 to 0° C. While maintaining the reaction mixture at this temperature, AlCl3 (3.30 eq) was added portion-wise to the reaction. The reaction was stirred at a temperature of 0 to 5° C. for about 2 hours, then subsequently warmed to 20-25° C. The reaction was then quenched with water (6.5 fold; v/w of starting material) and the mixture acidified to a pH of 2 with 2.0M HCl. The organic layer was then collected and the aqueous layer washed with CH2Cl2 to recover remaining product. The organic layers were combined and washed with 1.0M HCl and water followed by a brine wash and concentrated in vacuo. Ethyl acetate (1.0 fold; v/w of starting material) was added to the solid and heated to dissolve the product. The flask was gradually cooled to 0-2° C. followed by the slow addition of hexanes. The mixture was agitated for a period of about 2 hours, followed by filtration to collect the solid. The solid was subsequently dried under vacuum.

Provenance & Evidence