2,2-difluoro-2-phenylacetamide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,2-Difluoro-2-phenylacetamide (2.4 g, 14 mmol), as prepared in the preceding step, was dissolved in tetrahydrofuran (30 mL) and cooled to 0° C. To this stirred solution was added 1.0 M borane in tetrahydrofuran (35 mL, 35 mmol) dropwise in 30 minutes, and the reaction mixture was refluxed for 16 hours. After cooling to room temperature, a solution of potassium carbonate (5 g) in water (20 mL) was added to the reaction mixture. The mixture was concentrated in vacuo to about 50 mL and extracted with dichloromethane (3×50 mL). The dichloromethane layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was then purified by flash column chromatography (1:1 ethyl acetate:hexane) to give the title compound as a pale yellow oil (900 mg, 41%). 1H NMR (400 MHz, CDCl3) δ 7.45 (m, 5H), 3.18 (t, 2H, J=14.5 Hz), 1.60 (s(br), 2H). the reaction mixture was refluxed for 16 hours After cooling to room temperature The mixture was concentrated in vacuo to about 50 mL extracted with dichloromethane (3×50 mL) The dichloromethane layer was washed with brine dried over Na2SO4 concentrated in vacuo The residue was then purified by flash column chromatography (1:1 ethyl acetate:hexane)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,2-Difluoro-2-phenylacetamide (2.4 g, 14 mmol), as prepared in the preceding step, was dissolved in tetrahydrofuran (30 mL) and cooled to 0° C. To this stirred solution was added 1.0 M borane in tetrahydrofuran (35 mL, 35 mmol) dropwise in 30 minutes, and the reaction mixture was refluxed for 16 hours. After cooling to room temperature, a solution of potassium carbonate (5 g) in water (20 mL) was added to the reaction mixture. The mixture was concentrated in vacuo to about 50 mL and extracted with dichloromethane (3×50 mL). The dichloromethane layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was then purified by flash column chromatography (1:1 ethyl acetate:hexane) to give the title compound as a pale yellow oil (900 mg, 41%). 1H NMR (400 MHz, CDCl3) δ 7.45 (m, 5H), 3.18 (t, 2H, J=14.5 Hz), 1.60 (s(br), 2H). the reaction mixture was refluxed for 16 hours After cooling to room temperature The mixture was concentrated in vacuo to about 50 mL extracted with dichloromethane (3×50 mL) The dichloromethane layer was washed with brine dried over Na2SO4 concentrated in vacuo The residue was then purified by flash column chromatography (1:1 ethyl acetate:hexane)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following the procedures described in Middleton and Bingham J. Org. Chem., 1980, 45, 2883, 500 mg portion of 7-5 (4.826 mmol) was dissolved in 25 ml of THF and cooled to 0° C. via ice bath. To this stirred solution was added 30 ml (30 mmol) of 1M Borane·THF complex dropwise over ten mintes via syringe. The reaction mixture was aged until the ice bath expired. Upon expiration of the ice bath, the reaction mixture was heated to 70° C. overnight. The reaction mixture was diluted with water and concentrated in vacuo. The residue was diluted with chloroform and washed with 10% sodium carbonate. Three chloroform extractions were performed on the aqueous layer. The organic layers were combined, dried (sodium sulfate), and concentrated in vacuo to give 450 mg of a yellow oil. The oil was purified using a 30mm column, 5 inches of silica gel, and a 1:1 ethyl acetate to hexane solvent system to give 7-6 (Wade and Kheribet J. Org. Chem, 1980, 45, 5333) as a yellow oil: H1NMR CDCl3): δ 3.15 (t, 2H, 14.6 Hz), 7.4-7.49 (m, 5H). To this stirred solution was added 30 ml (30 mmol) of 1M Borane·THF complex dropwise over ten mintes via syringe concentrated in vacuo The residue was diluted with chloroform washed with 10% sodium carbonate Three chloroform extractions dried (sodium sulfate) concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a s solution of 2,2-difluoro-2-phenyl-acetamide (0.76 g, 4.4 mmol) in THF (5 mL) is added Borane in THF (1 M, 20 mL, 20 mmole) at 10° C. After 70° C. for 20 h, the mixture is quenched with water (10 mL), concentrated, and chromatographed on SiO2 eluting with 90% EtOAc in heptane to afford 2,2-difluoro-2-phenyl-ethylamine (0.58 g). LCMS: RT 0.92 minutes; MS: 158 (M+H); 1H NMR (300 MHz, CDCl3) □7.57-7.45 (5H, m), 3.2 (2H, t). the mixture is quenched with water (10 mL) concentrated chromatographed on SiO2 eluting with 90% EtOAc in heptane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of the above difluoro-phenyl-acetic acid ethyl ester and NH3 in MeOH (7 M, 10 mL) is heated to 60° C. for 2 h in a pressure tube. The mixture is cooled to room temperature, and concentrated to afford 2,2-difluoro-2-phenyl-acetamide (0.33 g). LCMS: RT=1.7 minutes; MS: 172 (M+H). concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a s solution of 2,2-difluoro-2-phenyl-acetamide (0.76 g, 4.4 mmol) in THF (5 mL) is added Borane in THF (1 M, 20 mL, 20 mmole) at 10° C. After 70° C. for 20 h, the mixture is quenched with water (10 mL), concentrated, and chromatographed on SiO2 eluting with 90% EtOAc in heptane to afford 2,2-difluoro-2-phenyl-ethylamine (0.58 g). LCMS: RT 0.92 minutes; MS: 158 (M+H); 1H NMR (300 MHz, CDCl3) □7.57-7.45 (5H, m), 3.2 (2H, t). the mixture is quenched with water (10 mL) concentrated chromatographed on SiO2 eluting with 90% EtOAc in heptane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of the above difluoro-phenyl-acetic acid ethyl ester and NH3 in MeOH (7 M, 10 mL) is heated to 60° C. for 2 h in a pressure tube. The mixture is cooled to room temperature, and concentrated to afford 2,2-difluoro-2-phenyl-acetamide (0.33 g). LCMS: RT=1.7 minutes; MS: 172 (M+H). concentrated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a s solution of 2,2-difluoro-2-phenyl-acetamide (0.76 g, 4.4 mmol) in THF (5 mL) is added Borane in THF (1 M, 20 mL, 20 mmole) at 10° C. After 70° C. for 20 h, the mixture is quenched with water (10 mL), concentrated, and chromatographed on SiO2 eluting with 90% EtOAc in heptane to afford 2,2-difluoro-2-phenyl-ethylamine (0.58 g). LCMS: RT=0.92 minutes; MS: 158 (M+H); 1H NMR (300 MHz, CDCl3) □7.57-7.45 (5H, m), 3.2 (2H, t). the mixture is quenched with water (10 mL) concentrated chromatographed on SiO2 eluting with 90% EtOAc in heptane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of the above difluoro-phenyl-acetic acid ethyl ester and NH3 in MeOH (7 M, 10 mL) is heated to 60° C. for 2 h in a pressure tube. The mixture is cooled to room temperature, and concentrated to afford 2,2-difluoro-2-phenyl-acetamide (0.33 g). LCMS: RT=1.7 minutes; MS: 172 (M+H). concentrated