General procedure for the synthesis of (5-chloro-2-pyridyl)methanol from methyl 5-chloropyridine-2-carboxylate:
1. Synthesis of intermediate 2: (5-chloro-2-pyridyl)methanol
- Methyl 5-chloro-2-pyridinecarboxylate (43 g, 251 mmol) was dissolved in methanol (400 mL) at 0 °C.
- NaBH4 (28.7 g, 754 mmol) was added to the above solution in small portions over about 30 min.
- After addition, the reaction mixture was stirred at room temperature for 2 h. The completion of the reaction was confirmed by TLC analysis.
- After completion of the reaction, the mixture was concentrated under reduced pressure and the residue was adjusted to pH 1 with 1N HCl.
- The resulting solution was extracted with EtOAc (3 x 300 mL) and the organic layers were combined.
- The organic layer was dried with Na2SO4 and the solvent was evaporated.
- The residue was purified by silica gel column chromatography using 10:1 petroleum ether/EtOAc as eluent to afford the title compound (5-chloro-2-pyridyl)methanol (36 g, 99%). Product Characterization: 1H NMR (1H NMR).
- Product characterization: 1H NMR (400 MHz, CDCl3) δ ppm 8.44 (d, J = 1.60 Hz, 1H), 7.62 (dd, J = 8.40, 2.40 Hz, 1H), 7.25 (d, J = 8.40 Hz, 1H), 4.69 (s, 2H), 3.83 (s, 1H).
