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

Participants

Reaction Conditions

Reaction Steps

In flask 1, a mixture of sodium iodide (171.6 mg, 1.14 mmol) in xylene (12.5 mL), acetic acid (12.5 ml) and acetic anhydride (4.2 mL, 44.54 mmoles) was heated to 97° C. In flask 2, acetic anhydride (4.2 mL, 44.5 mmol) 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 (10 g, 22.3 mmol corrected for assay) in xylene (12.5 mL) and acetic acid (12.5 ml) at ambient temperature. The mixture in flask 2 was added to the mixture in flask 1 over 2-3 hours maintaining the temperature at 97° C. The reaction was held at this temperature for a further 2 hours following the end of the addition. The reaction was cooled to 60° C. and split into 2 equal size portions. One of these portions was cooled to r.t. and propan-1-ol (25 mL) was added, following by water (25 mL), added over 15 minutes, effecting a precipitation. After stirring for 1 h, the solid product was collected by filtration, washed with propan-1-ol (2×10 mL) 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; 4.32 g (91% based on work up of half of the reaction mixture). Purity by HPLC 97.15 area %.

Provenance & Evidence