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

Participants

Reaction Conditions

Reaction Steps

Under protective gas atmosphere (argon), 23.1 g (0.398 mol) of dry potassium fluoride and 75.7 g (0.398 mol) of copper(I) iodide were titrated together and heated to 220° C. under high vacuum with agitation for 10 minutes until a slightly greenish colouration appeared. A reaction flask was initially charged under protective gas atmosphere (argon) with the calcined mixture of potassium fluoride and copper(I) iodide together with 170 ml of absolute NMP and 170 ml of absolute DMF, and 86 g (0.199 mol) of 4-chloro-1-(toluene-4-sulphonyl)-3-iodo-1H-pyrrolo[2,3-b]pyridine were subsequently introduced in portions at 20° C. with stirring to form a light grey suspension. 62.1 g (0.437 mol) of trimethyltrifluoromethylsilane were added dropwise to the reaction mixture within 20 minutes and the mixture was left to stir at 20° C. for 18 h. On completion of conversion (GC monitoring of conversion), the reaction mixture was added to 2000 ml of methyl tert-butyl ether, the organic phase was decanted and the residue was dispersed once more with 1000 ml of methyl tert-butyl ether. The combined organic phases were washed three times with 2000 ml each time of water and subsequently dried over MgSO4. Filtration and removal of the volatile constituents in a water-jet vacuum resulted in 50.1 g (0.134 mol; 67%) of 4-chloro-1-(toluene-4-sulphonyl)-3-trifluoromethyl-1H-pyrrolo[2,3-b]pyridine as a beige solid.

Provenance & Evidence