Acetic Anhydride → (4-Chloro-3,5-dimethylpyridin-2-YL)methanol

Participants

Reaction Conditions

Reaction Steps

At 90-95° C., a solution of 4-chloro-2,3,5-trimethylpyridine-N-oxide (60.0 g, 350 mmol) in toluene (920 mL), which was kept at about 60° C., was added over 7 h to acetic anhydride (232 mL). Under vacuum at about 60° C., the reaction mixture was concentrated until 820 mL had been distilled off. Toluene (840 mL) was added and, again, solvents were distilled off (940 mL). Then, toluene (180 mL) and 40% aqueous NaOH (80 mL) were added before the reaction mixture was heated at 50° C. for about 15 h. After addition of saturated aqueous sodium bicarbonate (120 mL), the phases were separated and the aqueous layer was extracted once more with toluene (80 mL). Finally, the combined organic phase was washed with saturated aqueous sodium bicarbonate (120 mL) and evaporated to dryness to give 4-chloro-2-hydroxymethyl-3,5-dimethylpyridine as a brownish oil which solidified upon standing; yield 61.8 g (quantitative).

Provenance & Evidence