Sodium Iodide → [4-acetylamino-3-(4-chlorophenylsulfanyl)-2-methyl-1H-indol-1-yl]acetic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of sodium iodide (0.0625 mol equiv) in xylene (1.99 rel vol), acetic acid (0.27 rel vol) and acetic anhydride (1.27 mole equiv) was heated to 102.5° C. in vessel 1 with stirring. In vessel 2, acetic anhydride (1.27 mole equiv) was added to a stirred slurry of ethyl [3-(4-chlorophenylsulfanyl)-4-(hydroxyimino)-2-methyl-4,5,6,7-tetrahydro-1H-indol-1-yl]acetate (1 mole equiv, limiting reagent) in xylene (2.24 rel vol) and acetic acid (0.27 rel vol) at 22° C. After stirring at this temperature for 30 mins, this mixture was added to the contents of reaction vessel 1 over 50 mins maintaining the temperature at 102.5° C. The reaction was held at this temperature for a further 2.5 h. The reaction was cooled to 60° C. and sodium thiosulfate (0.05 mole equiv) and water (0.5 rel vol) were added. After mixing, and allowing the layers to separate, the lower aqueous layer was discarded then the organic layer was distilled under vacuum, removing 1.8 rel vol distillate. The temperature was adjusted to 95° C. and the product precipitated by the addition of heptanes (3 rel vol). The suspension was cooled to 20° C. over 1 h then the solid product was collected by filtration, washed with ethanol (2 rel vol) and dried in vacuo at 40° C. to afford crude ethyl [4-acetylamino-3-(4-chlorophenylsulfanyl)-2-methyl-1H-indol-1-yl]acetate as a solid; 81% yield; purity by UHPLC 98.3 area %.

Provenance & Evidence