5-Trifluoromethyl-2-oxindole

Preparation

STEP A:Preparation of 5-trifluoromethyl-3-methylthio-oxindole To a solution of 15.4 g of p-trifluoromethylaniline in 400 ml. of methylene chloride cooled to minus 65℃. is added dropwise a solution of 10.2 g of t-butyl hypo chlorite in 20 ml. of methylene chloride. The solution is stirred at minus 65℃. for 5 minutes and there is then added dropwise 13.0 g of thioacetic acid ethyl ester in 20 ml of methylene chloride. The resulting mixture is stirred at minus 65℃. for 30 minutes. There is then slowly added 9.8 g of triethylamine and the reaction mixture allowed to warm to room temperature at which time 200 ml of 2 N. hydrochloric acid is added fol lowed by stirring overnight at room temperature. There is then added 20 ml of saturated sodium sulfite solution, the mixture stirred for 15 minutes, the aqueous phase separated and extracted into 1 N sodium hydroxide solution and treated with 6 N. hydrochloric acid to obtain a precipitate. The precipitate is then extracted into methylene chloride, dried, filtered and the methy lene chloride exchanged for ether and then pentane added to obtain 5-trifluoromethyl-3-methylthio-oxin dole, m.p. 136-138℃.STEP B: Preparation of 5-trifluoromethyl-oxindole A mixture of 4.0 g of 5-trifluoromethyl-3-methylthio oxindole, 20g of Raney Nickel and 100 ml. of methanol is refluxed for 4 days, cooled, treated with methylene chloride, filtered to remove the Raney Nickel and the filtrate concentrated in vacuo to obtain 5-trifluorometh yl-oxindole, m.p. 188-190℃.

Uses

5-(Trifluoromethyl)indolin-2-one is a useful reagent for the preparation of 3-Chloro-α-carbolines.