1-Methylpyrrolidine → 4-Chloro-1-(4-methylbenzene-1-sulfonyl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine

Participants

Reaction Conditions

Reaction Steps

Under an atmosphere of protective gas (argon), 23.1 g (0.398 mol) of dry potassium fluoride and 75.7 g (0.398 mol) of copper(I) iodide are ground with one another and, under high vacuum and with shaking, heated at 220° C. for 10 minutes, until there is a slight greenish discoloration. The sintered mixture of potassium fluoride and copper(1) iodide together with 170 ml of absolute N-methylpyrrolidine and 170 ml of absolute DMF is initially charged in a reaction flask under an atmosphere of protective gas (argon), and 86 g (0.199 mol) of 4-chloro-1-(toluene-4-sulfonyl)-3-iodo-1H-pyrrolo[2,3-b]pyridine are then added a little at a time and with stirring at 20° C., whereupon a light-gray suspension is formed. Over a period of 20 minutes, 62.1 g (0.437 mol) of trimethyltrifluoromethylsilane are added dropwise to the reaction mixture, and the mixture is stirred at 20° C. for 18 h. After complete conversion (conversion monitored by GC), the reaction mixture is poured into 2000 ml of methyl tert-butyl ether, the organic phase is decanted and the residue is once more dispersed in 1000 ml of methyl tert-butyl ether. The combined organic phases are washed three times with in each case 2000 ml of water and then dried over magnesium sulfate. Filtration and removal of the volatile components under water pump vacuum gives 50.1 g (67% of theory) of the target compound as a solid.

Provenance & Evidence