Application
3-Fluoropyridine-2-methanol is a pharmaceutical intermediate used to synthesize compounds with other applications. For example, 3-fluoropyridine-2-methanol can be used as a starting material to synthesize a tetrahydrocarbazole derivative that can be used as an androgen receptor modulator, with the following structure:
Dissolve 215 mg (1.69 mmol) of 3-fluoropyridine-2-methanol in 10 mL of dichloromethane and cool to 0 °C. Add thionyl chloride (160 μL, 2.20 mmol) and stir the reaction mixture for 1 hour. Add 50 mL of dichloromethane, and stir the reaction mixture with 2 × 40 mL of saturated sodium bicarbonate aqueous solution and 2 × 40 mL of brine. The organic fraction was separated and dried over magnesium sulfate, filtered, and concentrated under pressure to give 2-chloromethyl-3-fluoro-pyridine. Sodium hydride (60% in oil, 80 mg, 1.99 mmol) was then suspended in DMF (2 mL) and cooled to 0 °C. A solution of N-(6-cyano-2,3,4,9-tetrahydro-1H-carbazole-3-yl)-isobutyramide (253 mg, 0.90 mmol) in DMF (2 mL) was slowly added via syringe, and the mixture was stirred for 30 minutes, then warmed to ambient temperature for 60 minutes. 2-chloromethyl-5-fluoro-pyridine hydrochloride (180 mg, 0.99 mmol) was added, and the reaction mixture was stirred for approximately 12 hours. The reaction was quenched with a saturated aqueous solution of ammonium chloride (5 mL). Ethyl acetate (50 mL) was added, followed by water (50 mL) and washing with brine (2 × 50 mL). The organic phase was separated, dried over magnesium sulfate, filtered, and evaporated under reduced pressure. The resulting residue was ground with ether (10 mL) for 5 minutes and then filtered to obtain 187 mg (53%) of the above compound as a light yellow solid.
Definition
ChEBI: (3-Fluoropyrid-2-yl)methanol is a member of pyridines.
Synthesis
General procedure for the synthesis of 3-fluoropyridine-2-methanol from (6-bromo-3-fluoropyridin-2-yl)methanol: First, (6-bromo-3-fluoropyridin-2-yl)methanol (850 mg, 4.13 mmol) was dissolved in methanol (40 mL), followed by purging the solution with nitrogen. Next, palladium carbon (200 mg, 5% wet) was added and the reaction mixture was stirred under hydrogen atmosphere (2 balloons) for 20 hours. After completion of the reaction, the reaction mixture was filtered through Celite and the filter cake was washed with methanol. The filtrate was concentrated under reduced pressure and the resulting residue was dissolved in chloroform (150 mL). The organic phase was washed with saturated aqueous sodium bicarbonate (75 mL) and subsequently dried over magnesium sulfate, filtered and concentrated to afford 433 mg (82% yield) of 3-fluoropyridine-2-methanol, and the product was ready for use without further purification.1H NMR (300 MHz, CDCl3): δ 8.40 (m, 1H), 7.42-7.36 (m, 1H), 7.29- 7.23 (m, 1H), 4.84 (s, 2H), 3.97 (br s, 1H); MS (APCI): m/z 110 [C6H6FNO - H2O + H]+.
References
[1] Patent: WO2007/2181, 2007, A2. Location in patent: Page/Page column 165
