2-溴-6-氟苯乙腈

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 329 (3.89 g, 18.17 mmol) and concentrated sulfuric acid (35 mL) in ethanol (80 mL) was heated to reflux overnight. The mixture was allowed to cool down to room temperature, and poured into a mixture of ice/water, shaken for 15 min, and extracted with AcOEt. The extract was successively washed with water, sat. NaHCO3, water, dried over anhydrous magnesium sulfate, filtered, and concentrated to afford title compound 330 (4.86 g, quantitative yield, contaminated) as a yellow oily liquid. LCMS: 261.0 and 263.0 (M+H)+. to reflux overnight extracted with AcOEt The extract was successively washed with water, sat. NaHCO3, water dried over anhydrous magnesium sulfate filtered concentrated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A suspension of 2-bromo-6-fluorotoluene (5.00 g, 26.45 mmol), NBS (5.18 g, 29.10 mmol), and VAZO (323 mg, 1.32 mmol) in CCl4 (100 mL) was heated to reflux under vigoroue stirring overnight. The reaction mixture was cooled to room temperature, concentrated and the residue was removed by filtration. The filtrate was concentrated and the residue was re-dissolved in ethanol (90 mL), treated with a solution of NaCN (2.59 g, 52.9 mmol) in water (20 mL) and the combined mixture was heated to reflux for 5 hrs. Ethanol was removed under reduced pressure, the aqueous residue was diluted with water and extracted with AcOEt. The organic layer was successively washed with water and brine, concentrated, adsorbed on silica gel and purified by flash column chromatography (eluents AcOEt/hexanes: 10/90 to 20/80) to afford title compound 329 (3.92 g, 69% yield over 2 steps, slightly contaminated) as a pale yellow sticky solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 7.62-7.57 (m, 1H), 7.45-7.35 (m, 2H), 4.08 (s, 2H). was heated to reflux under vigoroue concentrated the residue was removed by filtration The filtrate was concentrated the residue was re-dissolved in ethanol (90 mL) the combined mixture was heated to reflux for 5 hrs Ethanol was removed under reduced pressure the aqueous residue was diluted with water extracted with AcOEt The organic layer was successively washed with water and brine concentrated purified by flash column chromatography (eluents AcOEt/hexanes: 10/90 to 20/80)