(2-CHLORO-PYRIDIN-4-YL)-METHANOL

58481-11-1

100704-10-7

The general procedure for the synthesis of 2-chloro-4-hydroxymethylpyridine from methyl 2-chloropyridine-4-carboxylate was as follows: 2-chloropyridine-4-methanol (reference Compound No. 7-1) was prepared with reference to Example 7. Under nitrogen protection, 0.95 M hexane solution of hydrogenated diisobutylaluminum (200 mL, 190 mmol) was slowly added dropwise to a solution of anhydrous tetrahydrofuran (300 mL) containing methyl 2-chloropyridine-4-carboxylate (11 g, 62 mmol), and the reaction mixture was stirred for 2 hr. under the cooling of an ice bath. Subsequently, 1N hydrochloric acid (200 mL) was added to the reaction system and stirring was continued for 1 hour at room temperature. Upon completion of the reaction, saturated aqueous sodium bicarbonate solution (400 mL) was added to neutralize and then extracted three times with ethyl acetate (100 mL). The organic phases were combined, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to remove the solvent to give 8.5 g of white solid 2-chloro-4-hydroxymethylpyridine in 95% yield. The structure of the product was confirmed by 1H-NMR (500 MHz, DMSO-d6): δ 4.56 (d, J = 5.8 Hz, 2H), 5.54 (t, J = 5.8 Hz, 1H), 7.34 (d, J = 4.9 Hz, 1H), 7.41 (s, 1H), 8.34 (d, J = 4.9 Hz, 1H).