反应详情

温度

50 °C

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.

1. temperaturemaintaining the temperature below 15° C
2. customThe cooling bath was removed
3. stirringwith stirring for 6 h
4. customDimethylformamide was removed by evaporation
5. dissolutionthe residue was dissolved in water (500 ml)
6. washThe emulsion was washed with dichloromethane (2×100 ml)
7. filtrationthe precipitate filtered off
8. washwashed with water to neutrality
9. customdried