2-(2,6-difluorophenyl)ethanamine

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

Procedure: A solution of 1,1'-thiocarbonyldiimidazole (9.5 g, 48 mmol) and 2-(2,6-difluorophenyl)ethylamine (7.54 g, 48 mmol) in acetonitrile (100 mL) was stirred at room temperature for 20 h. The solution was concentrated under reduced pressure and the resulting precipitate was collected by filtration and triturated with hexane to provide 16 g of crude titled product as a brown solid: The solution was concentrated under reduced pressure the resulting precipitate was collected by filtration triturated with hexane

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

Procedure: A solution of 2-(2,6-difluorophenyl)ethylamine (0.43 g, 2.7 mmol) and 1-[(2-pyridyl)thiocarbamoyl]imidazole (0.55 g, 2.7 mmol) in N,N-dimethylformamide (20 mL) was stirred at 90° C. for 27 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, 1N aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant oil was purified by chromatography on silica gel to provide 0.08 g (10%) of the titled product as a pale yellow solid: washed with water, 1N aqueous HCl, water, saturated sodium bicarbonate, and brine The organic layer was concentrated the resultant oil was purified by chromatography on silica gel

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

Procedure: 2,6-Difluorophenylacetonitrile (15.8 g, 100 mmol) was dissolved in tetrahydrofuran (75 mL) at room temperature. The solution was cooled in an ice bath and borane.THF complex (100mL, 100 mmol) was added dropwise over 15 minutes under nitrogen atmosphere. The ice bath was removed after borane addition was complete and the mixture was stirred at room temperature for 23 hours under nitrogen atmosphere. Saturated aqueous ammonium chloride solution (20 mL) was added dropwise with stirring over 30 minutes. The reaction mixture was filtered through diatomaceous earth, concentrated to an oil, redissolved in ethyl acetate/water, and adjusted to pH 1.0 with concentrated hydrochloric acid. The mixture was filtered through diatomaceous earth and the ethyl acetate layer extracted with 1N hydrochloric acid (4×10 mL). The combined acidic aqueous extracts were washed with ethyl acetate (2×50 ml). Solid sodium chloride was added to the acidic aqueous extracts, adjusted to pH 9.0 with solid sodium bicarbonate and 5N sodium hydroxide solution, and the mixture extracted with methylene chloride (7×50 mL). The combined methylene chloride extracts were washed with brine solution, dried over anhydrous sodium sulfate, filtered, and concentrated to yield 10.6 g (68%) of the titled product as a nearly colorless oil: The solution was cooled in an ice bath THF complex (100mL, 100 mmol) was added dropwise over 15 minutes under nitrogen atmosphere The ice bath was removed after borane addition Saturated aqueous ammonium chloride solution (20 mL) was added dropwise with stirring over 30 minutes The reaction mixture was filtered through diatomaceous earth concentrated to an oil redissolved in ethyl acetate/water The mixture was filtered through diatomaceous earth the ethyl acetate layer extracted with 1N hydrochloric acid (4×10 mL) The combined acidic aqueous extracts were washed with ethyl acetate (2×50 ml) Solid sodium chloride was added to the acidic aqueous extracts the mixture extracted with methylene chloride (7×50 mL) The combined methylene chloride extracts were washed with brine solution dried over anhydrous sodium sulfate filtered concentrated

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

Procedure: 2-(2,6-Difluorophenyl)acetonitrile (2.34 g, 15.28 mmol) was added to potassium boron hydride (3.29 g, 61.12 mmol) and Raney nickel (0.897 g, 15.28 mmol) in 50 mL of absolute ethanol while stirring. Then, vigorously stirring was continued at room temperature for 5 hrs. Then, vigorously stirring

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

Procedure: 2-(2,6-Difluorophenyl)acetonitrile (2.34 g, 15.28 mmol) was added to potassium boron hydride (3.29 g, 61.12 mmol) and Raney nickel (0.897 g, 15.28 mmol) in 50 mL of absolute ethanol while stirring. Then, vigorously stirring was continued at room temperature for 5 hrs. Then, vigorously stirring

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

Procedure: A solution of 1,1'-thiocarbonyldiimidazole (9.5 g, 48 mmol) and 2-(2,6-difluorophenyl)ethylamine (7.54 g, 48 mmol) in acetonitrile (100 mL) was stirred at room temperature for 20 h. The solution was concentrated under reduced pressure and the resulting precipitate was collected by filtration and triturated with hexane to provide 16 g of crude titled product as a brown solid: The solution was concentrated under reduced pressure the resulting precipitate was collected by filtration triturated with hexane

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

Procedure: A solution of 1,1'-thiocarbonyldiimidazole (9.5 g, 48 mmol) and 2-(2,6-difluorophenyl)ethylamine (7.54 g, 48 mmol) in acetonitrile (100 mL) was stirred at room temperature for 20 h. The solution was concentrated under reduced pressure and the resulting precipitate was collected by filtration and triturated with hexane to provide 16 g of crude titled product as a brown solid: The solution was concentrated under reduced pressure the resulting precipitate was collected by filtration triturated with hexane

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

Procedure: 2,6-Difluorophenylacetonitrile (15.8 g, 100 mmol) was dissolved in tetrahydrofuran (75 mL) at room temperature. The solution was cooled in an ice bath and borane THF complex (100mL, 100 mmol) was added dropwise over 15 minutes under nitrogen atmosphere. The ice bath was removed after borane addition was complete and the mixture was stirred at room temperature for 23 hours under nitrogen atmosphere. Saturated aqueous ammonium chloride solution (20 mL) was added dropwise with stirring over 30 minutes. The reaction mixture was filtered through diatomaceous earth, concentrated to an oil, redissolved in ethyl acetate/water, and adjusted to pH 1.0 with concentrated hydrochloric acid. The mixture was filtered through diatomaceous earch and the ethyl acetate layer extracted with 1N hydrochloric acid (4×10 mL). The combined acidic aqueous extracts were washed with ethyl acetate (2×50 ml). Solid sodium chloride was added to the acidic aqueous extracts, adjusted to pH 9.0 with solid sodium bicarbonate and 5N sodium hydroxide solution, and the mixture extracted with methylene chloride (7×50 mL). The combined methylene chloride extracts were washed with brine solution, dried over anhydrous sodium sulfate, filtered, and concentrated to yield 10.6 g (68%) of the titled product as a nearly colorless oil: The solution was cooled in an ice bath borane THF complex (100mL, 100 mmol) was added dropwise over 15 minutes under nitrogen atmosphere The ice bath was removed after borane addition Saturated aqueous ammonium chloride solution (20 mL) was added dropwise with stirring over 30 minutes The reaction mixture was filtered through diatomaceous earth concentrated to an oil redissolved in ethyl acetate/water The mixture was filtered through diatomaceous earch the ethyl acetate layer extracted with 1N hydrochloric acid (4×10 mL) The combined acidic aqueous extracts were washed with ethyl acetate (2×50 ml) Solid sodium chloride was added to the acidic aqueous extracts the mixture extracted with methylene chloride (7×50 mL) The combined methylene chloride extracts were washed with brine solution dried over anhydrous sodium sulfate filtered concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5.0 g (32.65 mmole) of 2,6-difluorophenylacetonitrile in 25 ml of anhydrous tetrahydrofuran at room temperature under nitrogen was added 33.0 ml (33.0 mmole) of 1.0 molar boranetetrahydrofuran complex by syringe. The mixture was stirred 4 hours, cooled in an ice bath, and quenched under nitrogen with a solution of 10.7 ml of concentrated hydrochloric acid in 22 ml of water. The mixture was heated to re flux, stirred I hr., and the tetrahydrofuran was removed by downward distillation. The milky white suspension was diluted with 22 ml of toluene and stirred 5 minutes longer. The layers were separated and the aqueous was extracted with 20 ml of hot toluene. The aqueous layer was cooled to 0° C., 50 ml of methylene chloride and 10 ml of 50% sodium hydroxide was added, and the layers were separated. The aqueous layer was extracted with methylene chloride (2×) and the combined organics were dried over sodium sulfate. Concentration gave 2.8 g (55%) of 2,6difluorophenethylamine as a light yellow liquid; 1H NMR (300 MHz, CDCl3) δ 7.10-7.30 (m, 1H), 6.80-7.00 (t, 2H), 2.80-3.00 (m, 2H), 2.70-2.80 (m, 2H), 1.35 (s, 2H) cooled in an ice bath quenched under nitrogen with a solution of 10.7 ml of concentrated hydrochloric acid in 22 ml of water The mixture was heated stirred I hr , and the tetrahydrofuran was removed by downward distillation The milky white suspension was diluted with 22 ml of toluene stirred 5 minutes longer The layers were separated the aqueous was extracted with 20 ml of hot toluene 50 ml of methylene chloride and 10 ml of 50% sodium hydroxide was added the layers were separated The aqueous layer was extracted with methylene chloride (2×) the combined organics were dried over sodium sulfate Concentration