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

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Reaction Conditions

Reaction Steps

Under an atmosphere of protective gas (argon), 63.5 g (1.59 mol) of sodium hydride are suspended in 1000 ml of abs. THF. 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 is added dropwise, and the reaction mixture is, after the end of the addition, allowed to stir for 15 minutes. 358 g (1.88 mol) of p-toluenesulfonyl chloride are added a little at a time to the reaction mixture, so that the temperature is kept between 5 and 10° C. After the end of the addition, the mixture is allowed to warm to 20° C. and stirred at this temperature for another hour. After complete conversion (the conversion is monitored by TLC), 20 l of saturated sodium bicarbonate solution and 10 l of ethyl acetate are added to the reaction mixture, the mixture is extracted and the organic phase is separated off. The aqueous phase is reextracted two more times with in each case 10 l of ethyl acetate and the organic phases are combined, dried and, under water pump vacuum, freed from volatile components. For purification of the crystalline crude product, the product is taken up in dichloromethane and chromatographed on silica gel (dichloromethane:petroleum ether=3:7). The solvents are removed under reduced pressure and the crystal slurry is triturated with diethyl ether, filtered off with suction and dried at 20° C. under high vacuum. 372 g (60% of theory) of the title compound are isolated as a solid.

Provenance & Evidence