4-(Trifluoromethyl)aniline → 3-Methylsulfanyl-5-trifluoromethyl-1,3-dihydro-indol-2-one

Participants

Reaction Conditions

Reaction Steps

To a solution of 30.8 of p-aminobenzotrifluoride predissolved in 450 ml. of methylene chloride, cooled to -58°C. (dry ice/isopropanol bath), and under an atmosphere of nitrogen, is added dropwise a solution of 21.1 ml. of t-butyl hypochlorite in 30 ml. of methylene chloride over 30 minutes while the reaction miture is maintained at -55° to 58°C. After the reaction mixture is stirred an additional five minutes, a solution of 25.6 g. of ethyl methylthioacetate in 30 ml. of methylene chloride is added dropwise over a period of 20 minutes while the reaction mixture is maintained at -55° to -58°C. The reaction mixture is stirred one hour at -55° to -65°C. and 60 ml. of methylene chloride is added to facilitate stirring. A solution of 25 ml. of triethylamine in 25 ml. of methylene chloride is added dropwise over a period of 10 minutes while the reaction mixture is maintained at -50°C. to -60°C. After an additional three minutes stirring, the cold bath is removed and the reaction mixture allowed to warm to 15°C. over a period of two hours; then 100 ml. of water is added. The organic phase is separated and concentrated in vacuo to an oil which is then dissolved in 100 ml. of ether. The ethereal solution is treated with 50 ml. of 2N hydrochloric acid, and the mixture is stirred overnight at room temperature. The phases are separated and the product is obtained in two portions by crystallization with cooling, followed by concentration of the mother liquors to a solid in vacuo. Recrystallization from ether/pentane gives 3-methylthio-5 -trifluoromethyl-2-indolinone, m.p. 136°-138°C.

Provenance & Evidence