58584-63-7

26218-80-4

58584-63-7

The general procedure for the synthesis of (6-methoxypyridin-3-yl)methanol from methyl 6-methoxynicotinate is as follows: Preparation Example 1: Synthesis of (6-methoxypyridin-3-yl)methanol (2) Methyl-6-methoxynicotinate (1) (650 g, 3.89 mol) was dissolved in tert-butyl methyl ether (MTBE, 6.5 L) and cooled in an ice bath under nitrogen protection. Sodium bis(2-methoxyethoxy) aluminum hydride (65% toluene solution, 1.45 kg, 4.67 mol) was slowly added to the reaction system over 1.5 hours. After addition, stirring was continued for 20 minutes. An aqueous 3.5N sodium hydroxide solution (2.6L) was slowly added while keeping the reaction temperature below 15°C. The reaction mixture was warmed up to 32°C and stirred for 45 minutes. After completion of the reaction, the organic layer was separated and the aqueous layer was extracted again with MTBE (2.3 L). The organic layers were combined and concentrated to dryness under reduced pressure. Toluene (1.3 L) was added to the residue and azeotropic distillation was performed. This azeotropic distillation process was repeated three times to give 597 g of the title compound as a light yellow oil (100% yield). 1H-NMR (CDCl3) δ (ppm): 8.11 (1H, d, J=2.4Hz), 7.62 (1H, dd, J=2.4Hz, 8.8Hz), 6.75 (1H, d, J=8.8Hz), 4.62 (2H, s), 3.93 (3H, s).