Sodium hydride → 1-(tetrahydropyran-4-yl)methyl-7-chloro-1H-indole-3-carboxylic acid

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Reaction Conditions

Reaction Steps

To a solution of 7-chloro-1H-indole-3-carboxylic acid (7.5 g, 38.0 mmol) in dimethyl-formamide (100 ml) at 10° C. under nitrogen was added sodium hydride (60% dispersion in mineral oil, 3.1 g, 76.0 mmol) portionwise over 10 mins, maintaining the temperature below 15° C. The cooling bath was removed and the suspension stirred for 90 mins. Toluene-4-sulfonic acid tetrahydropyran-4-ylmethylester (14.6 g, 53.0 mmol) was added. The mixture was heated at 50° C. with stirring for 6 h. Dimethylformamide was removed by evaporation and the residue was dissolved in water (500 ml). The emulsion was washed with dichloromethane (2×100 ml). The aqueous phase was acidified to pH 1 using 5 M hydrochloric acid and the precipitate filtered off, washed with water to neutrality and dried to afford 7-chloro-1-(tetrahydropyran-4-yl)methyl-1H-indole-3-carboxylic acid (15.0 g, 51.0 mmol) as a white solid.

Provenance & Evidence