Tetrahydrofuran → [2-(4-Fluoro-benzyl)-phenyl]-acetonitrile

関与物質

反応条件

反応手順

2-(4-fluoro-benzyl)-benzoic acid is dissolved in toluene (1.5 L/mol) and DMF (1 ml/mol) is added. The reaction mixture is heated up to 40° C. and thionyl chloride (1.1 eq.) is added. During the addition the reaction mixture is further heated up to 50° C. The reaction mixture is stirred at 50° C. during 2.5 hours, then evaporated at 50° C. under vacuum. THF (0.3 L/mol) is added and that solution is dropped into a 2 M NaBH4 solution in THF (1.5 eq.). The temperature rises to reflux (67° C.) and the reaction mixture is stirred at reflux during 2 hours. The reaction mixture is cooled down to room temperature. Acetone (350 ml/mol) is added (temperature rises to 40° C.), the reaction mixture is stirred during 30 minutes, followed by toluene (1 L/mol) and water (1.5 L/mol). The reaction mixture is heated up to 50° C. and the organic layer is evaporated at 50° C. under vacuum. CH2Cl2 (3 L/mol) is added, followed by triethylamine (1.1 eq.). SOCl2 (1.1 eq.) is added dropwise, the temperature rises to reflux. The reaction mixture is stirred during 45 min to room temperature. Water (1 L/mol) is added and the reaction mixture is stirred vigorously during 15 min. The organic layer is washed a second time with water (1 L/mol) and evaporated (40° C., vac.). The product is dissolved in toluene (2.5 L/mol), tetrabutylammonium hydrogenosulfate (phase-transfer catalyst) (0.1 eq.) is added at 70° C. and sodium cyanide 6 M (1.6 eq.) is added at 70° C. under vigorous stirring. The reaction mixture is then heated up to reflux and stirred during 3 hours. After cooling down to room temperature, water (0.5 L/mol) is added and the reaction mixture is stirred during 30 minutes. After washing a second time with water (0.5 L/mol), drying on magnesium sulphate and evaporating the solvent, [2-(4-fluoro-benzyl)-phenyl]-acetonitrile is obtained. Active yield: 94%. N.B. The product can be purified with e.g. thin-film distillation.

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