3-(2-fluorophenyl)propanenitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-(2-fluorophenyl) propionitrile (9.11 g) in tetrahydrofuran (200 mL) was heated to reflux and treated with borane-methyl sulfide complex (6 mL of ˜10 M, 60 mmol). Approximately half of the volume of the reaction was then distilled off. The mixture was then cooled in a −15° C. bath and treated dropwise with ice water (100 mL). The mixture was then concentrated to a solid. The solid was then dissolved in water (100 mL) and treated with concentrated (12 N)HCl (50 mL). The mixture was heated at reflux for 1 h, cooled to ambient temperature, and equilibrated with diethyl ether (100 mL). The organic solution was removed and the resulting aqueous mixture, cooled by the addition of ice, and then basified (pH>10) by treatment with 10 N NaOH (70 mL). The resulting solution was extracted with diethyl ether (100 mL). The diethyl ether extract was removed, dried over anhydrous MgSO4, filtered and concentrated to afford 3-(2-fluorophenyl)propylamine (3.62 g (41% from 2-fluorobenzaldehyde)). GC/MS gave: m/z (rel.int.) 153 (M+, 10), 136 (100), 109 (50), and 83 (22). to reflux treated with borane-methyl sulfide complex (6 mL of ˜10 M, 60 mmol) Approximately half of the volume of the reaction was then distilled off treated dropwise with ice water (100 mL) The mixture was then concentrated to a solid The solid was then dissolved in water (100 mL) treated with concentrated (12 N)HCl (50 mL) The mixture was heated at reflux for 1 h cooled to ambient temperature The organic solution was removed the resulting aqueous mixture, cooled by the addition of ice The resulting solution was extracted with diethyl ether (100 mL) The diethyl ether extract was removed dried over anhydrous MgSO4 filtered concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of the cis/trans mixture of 3-(2-fluorophenyl)acrylonitrile (9.36 g) in ethanol (100 mL) was treated with Pearlman's catalyst (palladium hydroxide, 1 g, 20% Pd by wt. dry) and the mixture shook vigorously under 60 p.s.i. hydrogen for 30 minutes. The mixture was filtered and the filtrate concentrated to afford 3-(2-fluorophenyl) propionitrile (9.11 g). GC/MS gave: m/z (rel.int.) 149 (M+, 19), 109 (100) and 83 (15). The mixture was filtered the filtrate concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(2-fluoro-phenyl)-ethanol (10.00 g, 71.50 mmol) in CH2Cl2 at 0° C. was added Et3N (20.00 mL, 0.14 mol) followed by MsCl (19.00 mL, 0.25 mol). The resulting mixture was stirred for 1 hour, then washed with H2O (3×100 mL) and brine (1×150 mL), dried over MgSO4 and concentrated. The residue was dissolved in DMF and KCN (9.30 g, 0.14 mol) was added. The resulting mixture was stirred at 75° C. for 14 hours. After cooling to room temperature, the reaction mixture was quenched into water and extracted with Et2O (3×300 mL). The combined organic extracts were washed with H2O (2×200 mL), brine (1×200 mL), dried over MgSO4 and concentrated to give the title compound. washed with H2O (3×100 mL) and brine (1×150 mL) dried over MgSO4 concentrated The residue was dissolved in DMF The resulting mixture was stirred at 75° C. for 14 hours the reaction mixture was quenched into water extracted with Et2O (3×300 mL) The combined organic extracts were washed with H2O (2×200 mL), brine (1×200 mL) dried over MgSO4 concentrated