The general procedure for the synthesis of (4-chloro-3,5-dimethylpyridin-2-yl)methanol from 4-chloro-2,3,5-trimethylpyridine-1-oxide was as follows: 4-chloro-2,3,5-trimethylpyridine-N-oxide (60.0 g, 350 mmol) was dissolved in toluene (920 mL) and heated to 90-95 °C. Maintaining the temperature at about 60 °C, acetic anhydride (232 mL) was slowly added and the reaction lasted for 7 hours. Subsequently, the reaction mixture was concentrated under vacuum at about 60°C until 820 mL of solvent was distilled. Toluene (840 mL) was added and the solvent (940 mL) was again distilled off. Next, toluene (180 mL) and 40% NaOH aqueous solution (80 mL) were added and the reaction mixture was heated at 50°C for about 15 hours. After the reaction was completed, saturated aqueous sodium bicarbonate solution (120 mL) was added to separate the organic and aqueous phases. The aqueous phase was extracted again with toluene (80 mL). The organic phases were combined, washed with saturated aqueous sodium bicarbonate (120 mL), and then evaporated to dryness to afford 4-chloro-2-hydroxymethyl-3,5-dimethylpyridine as a brown oil, which solidified on standing. The yield was 61.8 g (quantitative). The product was analyzed by 1H-NMR (200 MHz, DMSO-d6) and LC-MS to confirm: 1H-NMR δ= 2.30 (s, 3H), 2.36 (s, 3H), 4.58 (br s, 2H), 5.11 (br s, 1H), 8.27 (s, 1H); LC-MS: MH+ = 172/174.
