Hydrochloric Acid → (6-Chloropyridin-3-yl)methanol

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Reaction Steps

6-Chloronicotinic acid (3.0 g, 18.98 mmol) is dissolved in 30 ml of tetrahydrofuran (THF), with the temperature of the solution maintained below 30°. A 1 M solution of borane/TMF (19 ml, 19.0 mmol) is added at a rate to maintain a slow evolution of gas. This mixture is stirred at RT overnight. The reaction is poured onto approximately 50 g ice with 2 ml concentrated hydrochloric acid and is stirred for 1 hour. The pH of the reaction is adjusted to 5. The reaction is then extracted with chloroform, washed with water, dried and stripped to give 6-chloro-3-pyridinemethanol. A mixture of this pyridinemethanol (2.5 g, 17.4 mmol) and 1-fluoro- 4-nitrobenzene (2.4 g, 17.4 mmol), dissolved together in 15 ml of THF, is added to a stirring suspension of sodium hydride (0.42 g, 17.4 mmol) in 25 ml of THF at a rate to maintain the temperature below 32° . The mixture is stirred for 1 hour, then diluted with water, extracted with chloroform, washed with water, dried and stripped to give 2-chloro-5-(4-nitrophenoxy)methylpyridine.

Provenance & Evidence