4-Toluenesulfonyl chloride → 4-Chloro-3-iodo-1-(4-methylbenzene-1-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

Participants

Reaction Steps

Under protective gas atmosphere (argon), 63.5 g (1.59 mol) of sodium hydride were suspended in 1000 ml of abs. THF. To this were added dropwise with cooling at a temperature of 0-5° C. a solution of 402 g (1.44 mol) of 4-chloro-3-iodo-1H-pyrrolo[2,3-b]pyridine in 3000 ml of abs. THF, and the reaction mixture was left to stir for a further 15 minutes after completion of addition. Subsequently, 358 g (1.88 mol) of p-toluenesulphonyl chloride were added in portions to the reaction mixture in such a way that the temperature was kept between 5-10° C. After the addition had ended, the mixture was allowed to come to 20° C. and stirred at this temperature for a further hour. On completion of conversion (TLC monitoring of conversion), the reaction mixture was admixed with 20 l of saturated NaHCO3 solution and 10 l of ethyl acetate, and extracted, and the organic phase was removed. The aqueous phase was extracted twice more with 10 l each time of ethyl acetate, and the organic phases were combined, dried and freed of volatile constituents in a water-jet vacuum. To purify the crystalline crude product, it was taken up in dichloromethane and chromatographed using silica gel (CH2Cl2: 40/60 petroleum ether=3:7). After the solvents had been removed, the crystal slurry was extractively stirred in diethyl ether, and the solids were filtered off with suction and dried at 20° C. under high vacuum. A total of 372 g (0.86 mol, 60%) of 4-chloro-1-(toluene-4-sulphonyl)-3-iodo-1H-pyrrolo[2,3-b]pyridine were isolated as a colourless solid.

Provenance & Evidence