反应详情

To a suspension of potassium hydroxide (113 g, 2 mol) in DMSO (800 ml) was added 53.9 g, (0.49 mmol) 5-hydroxy-2-methylpyridine and the mixture stirred for 1 h. To this was added CH3I (34 ml, 0.55 mol) and the reaction mixture was stirred for one hour, then poured into water (2400 ml) and extracted with ether (1000 ml×5). The combined organic layers were washed with water and brine, dried over Na2SO4 and concentrated in vacuo to provide 5-methoxy-2-methylpyridine as a yellow oil. 1H NMR: (400 MHz, CDCl3) δ 8.19 (d, J=2.8 Hz, 1H), 7.14 (dd, J=8.8, 3.8 Hz, 1H), 7.08 (d, J=8.4 Hz, 1H), 3.83 (s, 3H), 2.65 (s, 3H). (5-methoxypyridin-2-yl)methanol: To a 0° C. solution of 10 g (72 mmol) 5-methoxy-2-methylpyridine in CHCl3 (50 ml) was slowly added 20 g (93.9 mmol) mCPBA and the mixture was stirred at room temperature for 16 h. The mixture was neutralized with excess sat. NaHSO3 solution. The aqueous layer was extracted with CHCl3 three times. The combined organic layers were dried over MgSO4 and evaporated to give 7 g of 5-methoxy-2-methyl-1-oxopyridine as a yellow solid. This was added slowly to hot (1000° C.)acetic anhydride (25 mL, 26 mmol) over 30 minutes and the mixture heated an additional 30 minutes, whereupon ethanol was added until the excess acetic anhydride was consumed. The mixture was cooled, concentrated, and neutralized with aqueous KHCO3 solution. The aqueous layer was extracted with CH2Cl2, dried over MgSO4, and concentrated in vacuo to afford 7.5 of (5-methoxypyridin-2-yl)methyl acetate as a dark oil. To this oil was added 25 mL of concentrated HCl and the mixture heated to reflux for 1 hour then concentrated in vacuo. The residue was treated with aqueous KHCO3 and extracted with CH2Cl2. The CH2Cl2 extract was dried over MgSO4, filtered, and concentrated in vacuo to give (5-methoxypyridin-2-yl)methanol as an oil. 1H NMR (400 MHz, DMSO-d6) δ 7.65 (m, 2H), 6.45 (m, 1H), 4.75 (s, 2H), 3.25 (s, 3H).

1. stirringthe reaction mixture was stirred for one hour
2. extractionextracted with ether (1000 ml×5)
3. washThe combined organic layers were washed with water and brine
4. dry with materialdried over Na2SO4
5. concentrationconcentrated in vacuo