The general procedure for the synthesis of 2-hydroxyethylpyridine from 2-chloromethylpyridine and formaldehyde is as follows: a two-necked Schlenk flask equipped with a magnetic stirring bar and a septum is heated under high vacuum with a hot air gun (ca. 400 °C) for 10 minutes. After cooling to room temperature, the flask was rinsed with argon (3 times). Zinc powder (654 mg, 2.0 equiv, 10.0 mmol) and THF (20 mL) were added sequentially. 1,2-dibromoethane (5 mol%) was added and the reaction mixture was heated to boiling. After cooling to room temperature, chlorotrimethylsilane (1 mol %) was added and the mixture was heated again to boiling. The flask was cooled to room temperature again, a solution of 2-chloromethylpyridine (633 mg, 5.0 mmol, 1 eq.) in THF (10 mL) was added and heated at 70 °C for 2 hours and then cooled to room temperature. Paraformaldehyde (450 mg, 3.0 eq, 15.0 mmol) was slowly added at room temperature and the flask was heated at 70 °C again for 6 hours. The reaction solution was cooled to room temperature and saturated NH4Cl solution was added. The phases were separated and the aqueous layer was extracted with ethyl acetate (100 mL). The organic layers were combined, washed sequentially with water (20 mL) and brine (10 mL) and dried over Na2SO4. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography using cyclohexane or cyclohexane/ethyl acetate as eluent to give 2-hydroxyethylpyridine (510 mg, 83%) as a colorless liquid.
