Uses
4-Cyano-2-fluorobenzyl alcohol is an essential drug intermediate and is widely applied to the synthesis of various drugs. For example: S1P1 Receptor agonists, drugs for treating Alzheimer's disease BMS708163, amides for treating arrhythmia, etc.
Synthesis
4-Cyano-2-fluorobenzyl alcohol, also known as 3-fluoro-4-hydroxymethylbenzonitrile, can be obtained by the reaction of 2-fluoro-4-bromobenzyl alcohol with zinc cyanide or by reduction of 4-cyano-2-fluorobenzoic acid methyl ester.
To a solution of 2-fluoro-4-bromobenzenemethanol (3.25 g, 15.85 mmol) in DMF (35 mL) was added zinc cyanide (1.85 g, 15.85 mmol), tetrakis(triphenylphosphine)palladium (Pd(PPh3) 4.0.916 g, 0.79 mmol), and the reaction was heated with argon deoxygenation for 16 hr. at 100 degrees C., cooled to Room temperature, diluted with ethyl acetate (100mL), washed by water (100mL3), saturated brine (100mL3), dried with anhydrous sodium sulfate and filtered, concentrated to crude, then purified by column chromatography (petroleum ether ~ ethyl acetate = 15/1 ~ 4/1 system elution) to obtain a white solid product (0.72g, yield 30%).
