ethyl 3-(dibenzylamino)-2,2-difluoropropanoate

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

実験手順: To a solution of ethyl 3-(dibenzylamino)-2,2-difluoropropanoate (517 mg, 1.55 mmol) in EtOH (1 mL) was added 0.5 N HCl (1 mL) and Pd(OH)2/C (20%, 50 mg). The reaction mixture was stirred at room temperature under H2 atmosphere for 3 days. The reaction mixture was filtered and the solid was rinsed with water and ether. The aqueous layer was separated from the ether layer and lyophilized to yield ethyl 3-amino-2,2-difluoropropanoic acid as a white solid (210 mg, 100% yield). 1H NMR (400 MHz, DMSO) ppm 3.27-3.46 (m, 2H), 8.06-8.64 (m, 3H). The reaction mixture was filtered the solid was rinsed with water and ether The aqueous layer was separated from the ether layer

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

実験手順: Ethyl 3-(dibenzylamino)-2,2-difluoropropanoate (5.00 g, 15.0 mmol) was dissolved in EtOH (25 mL) and trifluoroacetic acid was added (1.15 mL, 15.5 mmol). To this mixture, Pd(OH)2/C (20%, 250 mg) was added, and the reaction mixture was hydrogenated at 60 psi overnight. The mixture was filtered through a pad of Celite, the Celite pad was washed with ethanol and the filtrate was concentrated in vacuo. The residue was dissolved in THF (65 mL) and to the solution was added acetone (0.872 g, 15.0 mmol) and sodium acetate (1.23 g, 15.0 mmol). The reaction mixture was cooled to 0° C. and NaBH(OAc)3 (4.77 g, 22.5 mmol) was added in portions over 5 min. The mixture was stirred vigorously at room temperature overnight and then was poured into a cold (0° C.) brine solution (100 mL). The pH was adjusted to 12.5 with NaOH (50%) and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic extract were dried (MgSO4) and concentrated in vacuo to afford the title compound as a clear light yellow oil (1.54 g, 54%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.04 (d, J=6.32 Hz, 6H) 1.36 (t, J=7.20 Hz, 3H) 2.73-2.94 (m, 1H) 3.20 (t, J=13.52 Hz, 2H) 4.34 (q, J=7.24 Hz, 2H) was hydrogenated at 60 psi overnight The mixture was filtered through a pad of Celite the Celite pad was washed with ethanol the filtrate was concentrated in vacuo The residue was dissolved in THF (65 mL) and to the solution the mixture was extracted with ethyl acetate (3×50 mL) The combined organic extract were dried (MgSO4) concentrated in vacuo

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

実験手順: In a round bottom flask, Ethyl 3-(dibenzylamino)-2,2-difluoropropanoate (1.72 g, 5.2 mmol) was solubilized in EtOH (25 mL) and TFA added (0.4 mL, 5.5 mmol). Under an atmosphere of nitrogen Pd(OH)2/C (170 mg of 20% Pd by wt. wet) was added. The reaction mixture was repeatedly purged with nitrogen and then left under hydrogen overnight. At this point the reaction was deemed complete by LCMS, filtered through a pad of Celite, the pad washed with EtOH and the filtrate concentrated without heating to yield a foggy syrup which starts to crystallize upon standing (1.31 g, 94% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.29 (t, J=7.20 Hz, 3H) 3.72 (t, J=16.17 Hz, 2H) 4.34 (q, J=7.24 Hz, 2H). [M+H] calc'd for C5H9F2NO2, 154. found 154. Under an atmosphere of nitrogen Pd(OH)2/C (170 mg of 20% Pd by wt. wet) was added The reaction mixture was repeatedly purged with nitrogen filtered through a pad of Celite the pad washed with EtOH the filtrate concentrated without heating to yield a foggy syrup which to crystallize

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

実験手順: To a solution of ethyl 3-(dibenzylamino)-2,2-difluoropropanoate (517 mg, 1.55 mmol) in EtOH (1 mL) was added 0.5 N HCl (1 mL) and Pd(OH)2/C (20%, 50 mg). The reaction mixture was stirred at room temperature under H2 atmosphere for 3 days. The reaction mixture was filtered and the solid was rinsed with water and ether. The aqueous layer was separated from the ether layer and lyophilized to yield ethyl 3-amino-2,2-difluoropropanoic acid as a white solid (210 mg, 100% yield). 1H NMR (400 MHz, DMSO) ppm 3.27-3.46 (m, 2H), 8.06-8.64 (m, 3H). The reaction mixture was filtered the solid was rinsed with water and ether The aqueous layer was separated from the ether layer

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

実験手順: In a round bottom flask, ethyl 3-(dibenzylamino)-2,2-difluoropropanoate (1.72 g, 5.2 mmol) was solubilized in EtOH (25 mL) and TFA added (0.4 mL, 5.5 mmol). Under an atmosphere of nitrogen Pd(OH)2/C (170 mg of 20% Pd by wt. wet) was added. The reaction mixture was repeatedly purged with nitrogen and then left under hydrogen overnight. At this point the reaction was deemed complete by LCMS, filtered through a pad of Celite, the pad washed with EtOH and the filtrate concentrated without heating to yield ethyl 3-amino-2,2-difluoropropanoate, as its TFA salt, as a foggy syrup which starts to crystallize upon standing (1.31 g, 94% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.29 (t, J=7.20 Hz, 3 H) 3.72 (t, J=16.17 Hz, 2 H) 4.34 (q, J=7.24 Hz, 2 H). [M+H] calc'd for C5H9F2NO2, 154; found 154. Under an atmosphere of nitrogen Pd(OH)2/C (170 mg of 20% Pd by wt. wet) was added The reaction mixture was repeatedly purged with nitrogen filtered through a pad of Celite the pad washed with EtOH the filtrate concentrated without heating

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

実験手順: In a round bottom flask, ethyl 3-(dibenzylamino)-2,2-difluoropropanoate (1.72 g, 5.2 mmol) was solubilized in EtOH (25 mL) and TFA added (0.4 mL, 5.5 mmol). Under an atmosphere of nitrogen Pd(OH)2/C (170 mg of 20% Pd by wt. wet) was added. The reaction mixture was repeatedly purged with nitrogen and then left under hydrogen overnight. At this point the reaction was deemed complete by LCMS, filtered through a pad of Celite, the pad washed with EtOH and the filtrate concentrated without heating to yield ethyl 3-amino-2,2-difluoropropanoate, as its TFA salt, as a foggy syrup which starts to crystallize upon standing (1.31 g, 94% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.29 (t, J=7.20 Hz, 3 H) 3.72 (t, J=16.17 Hz, 2 H) 4.34 (q, J=7.24 Hz, 2 H). [M+H] calc'd for C5H9F2NO2, 154; found 154. Under an atmosphere of nitrogen Pd(OH)2/C (170 mg of 20% Pd by wt. wet) was added The reaction mixture was repeatedly purged with nitrogen filtered through a pad of Celite the pad washed with EtOH the filtrate concentrated without heating

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

実験手順: Ethyl 3-(dibenzylamino)-2,2-difluoropropanoate (5.00 g, 15.0 mmol) was dissolved in EtOH (25 mL) and trifluoroacetic acid was added (1.15 mL, 15.5 mmol). To this mixture, Pd(OH)2/C (20%, 250 mg) was added, and the reaction mixture was hydrogenated at 60 psi overnight. The mixture was filtered through a pad of Celite, the Celite pad was washed with ethanol and the filtrate was concentrated in vacuo. The residue was dissolved in THF (65 mL) and to the solution was added acetone (0.872 g, 15.0 mmol) and sodium acetate (1.23 g, 15.0 mmol). The reaction mixture was cooled to 0° C. and NaBH(OAc)3 (4.77 g, 22.5 mmol) was added in portions over 5 min. The mixture was stirred vigorously at room temperature overnight and then was poured into a cold (0° C.) brine solution (100 mL). The pH was adjusted to 12.5 with NaOH (50%) and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic extract were dried (MgSO4) and concentrated in vacuo to afford the title compound as a clear light yellow oil (1.54 g, 54%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.04 (d, J=6.32 Hz, 6 H) 1.36 (t, J=7.20 Hz, 3 H) 2.73-2.94 (m, 1 H) 3.20 (t, J=13.52 Hz, 2 H) 4.34 (q, J=7.24 Hz, 2 H) was hydrogenated at 60 psi overnight The mixture was filtered through a pad of Celite the Celite pad was washed with ethanol the filtrate was concentrated in vacuo The residue was dissolved in THF (65 mL) and to the solution the mixture was extracted with ethyl acetate (3×50 mL) The combined organic extract were dried (MgSO4) concentrated in vacuo

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

実験手順: In a round bottom flask, Ethyl 3-(dibenzylamino)-2,2-difluoropropanoate (1.72 g, 5.2 mmol) was solubilized in EtOH (25 mL) and TFA added (0.4 mL, 5.5 mmol). Under an atmosphere of nitrogen Pd(OH)2/C (170 mg of 20% Pd by wt. wet) was added. The reaction mixture was repeatedly purged with nitrogen and then left under hydrogen overnight. At this point the reaction was deemed complete by LCMS, filtered through a pad of Celite, the pad washed with EtOH and the filtrate concentrated without heating to yield a foggy syrup which starts to crystallize upon standing (1.31 g, 94% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.29 (t, J=7.20 Hz, 3 H) 3.72 (t, J=16.17 Hz, 2 H) 4.34 (q, J=7.24 Hz, 2 H). [M+H] calc'd for C5H9F2NO2, 154; found 154. Under an atmosphere of nitrogen Pd(OH)2/C (170 mg of 20% Pd by wt. wet) was added The reaction mixture was repeatedly purged with nitrogen filtered through a pad of Celite the pad washed with EtOH the filtrate concentrated without heating to yield a foggy syrup which to crystallize

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

実験手順: To a solution of ethyl 3-(dibenzylamino)-2,2-difluoropropanoate (517 mg, 1.55 mmol) in EtOH (1 mL) was added 0.5 N HCl (1 mL) and Pd(OH)2/C (20%, 50 mg). The reaction mixture was stirred at room temperature under H2 atmosphere for 3 days. The reaction mixture was filtered and the solid was rinsed with water and ether. The aqueous layer was separated from the ether layer and lyophilized to yield ethyl 3-amino-2,2-difluoropropanoic acid as a white solid (210 mg, 100% yield). 1H NMR (400 MHz, DMSO) ppm 3.27-3.46 (m, 2H), 8.06-8.64 (m, 3H). The reaction mixture was filtered the solid was rinsed with water and ether The aqueous layer was separated from the ether layer

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

実験手順: To a solution of ethyl 3-(dibenzylamino)-2,2-difluoropropanoate (517 mg, 1.55 mmol) in EtOH (1 mL) was added 0.5 N HCl (1 mL) and Pd(OH)2/C (20%, 50 mg). The reaction mixture was stirred at room temperature under H2 atmosphere for 3 days. The reaction mixture was filtered and the solid was rinsed with water and ether. The aqueous layer was separated from the ether layer and lyophilized to yield ethyl 3-amino-2,2-difluoropropanoic acid as a white solid (210 mg, 100% yield). 1H NMR (400 MHz, DMSO) ppm 3.27-3.46 (m, 2H), 8.06-8.64 (m, 3H). The reaction mixture was filtered the solid was rinsed with water and ether The aqueous layer was separated from the ether layer