General procedure for the synthesis of 3-fluoro-5-(hydroxymethyl)-2-methylpyridine from trimethylcyclotriboroxane and (6-chloro-5-fluoro-pyridin-3-)methanol: (6-chloro-5-fluoro-3-pyridinyl)methanol (1.3 g, 8.05 mmol) was dissolved in 1,4-dioxane (10 ml), and sequentially added K2CO3 (3.34 g, 24.14 mmol ), trimethylcycloboroxane (1.125 ml, 8.05 mmol) and Pd(PPh3)4 (0.465 g, 0.402 mmol). The mixture was placed in a pressure tube and the reaction was heated at 110°C for 20 hours. After completion of the reaction, the reaction mixture was quenched with H2O, extracted with EtOAc and the organic phase was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by fast chromatography (Flashmaster II, 25g spherical silica gel column, eluent DCM/MeOH 98:2) to afford 560 mg of 3-fluoro-5-(hydroxymethyl)-2-methylpyridine and Ph3PO. To remove Ph3PO, the product was washed again with water and extracted with EtOAc. The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure to give 468 mg (39% yield) of 3-fluoro-5-(hydroxymethyl)-2-methylpyridine, the purity of which met the requirements of the subsequent reaction.1H-NMR (δ, ppm, CDCl3): 8.27 (d, 1H), 7.55 (dd, 1H), 4.74 (bs, 2H), 2.49 (s, 1H). 3H). [ES MS] m/z 142 (MH+).
