Synthesis
The general procedure for the synthesis of 2,6-dichloro-3-hydroxymethylpyridine from 2,6-dichloronicotinic acid was as follows: 2,6-dichloronicotinic acid (1000 mg, 5.21 mmol) was dissolved in anhydrous tetrahydrofuran (5 mL) and the solution was cooled to 0 °C. Borane-tetrahydrofuran complex (7.82 mL, 7.82 mmol, 1.0 M tetrahydrofuran solution) was slowly added under stirring. The reaction mixture was stirred overnight at room temperature. Subsequently, water (1 mL) and potassium carbonate were added and stirring was continued for 2 hours. After completion of the reaction, the mixture was filtered and the filtrate was concentrated to give the crude product. The crude product was purified by silica gel column chromatography with the eluent being a 10:90 to 20:80 ethyl acetate/hexane solvent mixture to give 2,6-dichloro-3-hydroxymethylpyridine (876 mg, 94% yield). The structure of the product was confirmed by 1H NMR (400 MHz, MeOH-d4): δ 7.96 (d, 1H, J = 8.0 Hz), 7.45 (d, 1H, J = 8.0 Hz), 4.64 (s, 2H).
References
[1] Patent: WO2006/44454, 2006, A1. Location in patent: Page/Page column 62
[2] Patent: WO2014/100695, 2014, A1. Location in patent: Paragraph 00408
[3] Patent: WO2006/85212, 2006, A2. Location in patent: Page/Page column 43
[4] Patent: US6573274, 2003, B1
