4-Toluenesulfonyl chloride → HCID 90421554, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-bromo-6-chloro-1H-indole-3-carboxylic acid methyl ester (80.0 g, 277 mmol) in N,N-dimethylformamide (600 mL) at 0° C. was added sodium hydride (60% dispersion in oil, 16.6 g, 416 mmol) portion-wise over 20 minutes. The reaction was stirred at 0° C. for 60 minutes followed by the addition of 4-methylbenzenesulphonyl chloride (63.4 g, 333 mmol), which was added portion-wise to the stirring solution. The reaction was allowed to stir for 2 hours at 0° C. and the ice bath was removed and the reaction was allowed to warm to room temperature and stirred overnight. The reaction was poured into water (1200 mL) and stirred for 12 hours. The suspension was filtered and the filter cake was washed with a further portion of water (700 mL) then heptane (2×300 mL), 160 g of crude material was recovered. The material was placed in a 3 L round bottom flask and placed on rotorary evaporated with a 40° C. bath under vacuum overnight to remove residual water. This afforded 116 g of pink solid which was suspended in acetone (600 mL) and heated to reflux for 1 hour, then removed from the heat, cooled to room temperature, and stirred for a further hour. The suspension was filtered and the filter cake was washed with acetone (˜500 mL) until the filtrate was colorless. The filter cake was dried to afford desired product (108.7 g, 89% yield). 1H NMR (CDCl3, 400 MHz) 5=8.39 (s, 1 H) 8.24 (s, 1 H) 8.11 (s, 1 H) 7.82 (d, J=8.59 Hz, 2 H) 7.32 (d, J=8.20 Hz, 2 H) 3.93 (s, 3 H) 2.40 (s, 3 H); MS (ES+) 441.9 (M+H)+.

Provenance & Evidence