Methanol → (2-Anilinopyridin-3-yl)methanol

Participants

Reaction Steps

To a refluxing solution of 6.5 g (30.4 mmole) of 2-phenylamino-3-pyridinecarboxylic acid and 7.5 mL (64.2 mmoles) of trimethylborate in 40 mL of THF under N2 was added dropwise, 65 mL (130 mmole) of 2M borane-methyl sulfide over a 30 min period. The reaction mixture was refluxed for 2 hrs, then cooled, and 50 mL of CH3OH was added dropwise with stirring over a period of 30 min. The mixture was refluxed for 5 min, and the solvents were evaporated to leave a gummy light yellow semi-solid which was partitioned between 250 mL of 2N HCl and 150 mL of CH2Cl2. The aqueous layer was separated and brought to pH 8 (NaHCO3), and the mixture was extracted with CH2Cl2 (700 mL). The CH2Cl2 was evaporated to leave 3.0 g of semi-solid which was purified by dry-column chromatography (glass column, 4×60 cm; 235 gm of silica; eluted with CH2Cl2). The fractions containing the product were extracted with CH2Cl2 then with CH3OH. The solvents were evaporated, and the oily residue was convened to the HCl salt in acetone-Et2O to give 1.4 g (40%) of cream-colored solid; mp 180°-182° C. (J. Med. Chem. 11, 894 (1968), mp 189°-190° C.). MS (EI) m/e (relative intensity): 200 (M+, 27), 199 (24), 182 (65), 181 (100).

Provenance & Evidence