2-(1-aminocyclobutyl)propan-1-ol

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

Procedure: A solution of 3-oxo-3-(2,3,4,5-tetrafluorophenyl)propionate (6.13 g, 23.2 mmol), Ac2O (13.2 mL, 0.140 mol) and triethyl orthoformate (7.80 mL, 46.8 mmol) was stirred at 120° C. for 3 hours. The mixture was concentrated in vacuo and dried under high vacuum. To the mixture of the residue in anhydrous toluene (100 mL) was slowly added 2-(1-aminocyclobutyl)propanol (3.00 g, 23.2 mmol) in anhydrous toluene (40 mL) at 0° C. The mixture was stirred at room temperature for 2 hours and the solvent was removed by evaporation. Flash chromatography (AcOEt:Hexane=1:1) of the residue gave the title compound as a colorless solid (6.23 g, 67%). 1H-NMR (400 MHz, CDCl3) δ 0.95 (0.6H, t, J=7.3 Hz), 0.97 (3H, d, J=7.3 Hz), 1.09 (2.4H, t, J=7.3 Hz), 1.54 (1H, t, J=4.9 Hz), 1.85-2.15 (3H, m), 2.19-2.50 (4H, m), 3.62-3.75 (2H, m), 4.02 (0.2H, q, J=7.3 Hz), 4.07 (0.8H, q, J=7.3 Hz), 6.97-7.13 (1H, m), 8.24 (0.8H, d, J=15.3 Hz), 8.25 (0.2H, d, J=15.3 Hz), 10.03 (0.2H, d, J=14.1 Hz), 11.40 (0.8H, d, J=14.1 Hz). The mixture was concentrated in vacuo dried under high vacuum To the mixture of the residue in anhydrous toluene (100 mL) at 0° C the solvent was removed by evaporation

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

Procedure: 10% Pd—C (700 mg) was added to a solution of 2-[1-(benzylamino)cyclobutyl]propanol (6.81 g, 31.1 mmol) in EtOH (150 mL) and the mixture was stirred under H2 gas 5 kgf/cm2 at room temperature for 6 hours. The mixture was filtered, and the filtrate was concentrated in vacuo. Distillation of the residue gave the title compound as a colorless oil (2.96 g, 74%). 1H-NMR (400 MHz, CDCl3) δ 1.03 (3H, d, J=7.3 Hz), 1.63-1.74 (3H, m), 1.78-1.94 (2H, m), 2.10-2.28 (2H, m), 3.50 (1H, dd, J=11.0 and 4.3 Hz), 3.91 (1H, dd, J=11.0 and 3.1 Hz). The mixture was filtered the filtrate was concentrated in vacuo Distillation of the residue

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

Procedure: 10% Pd—C (700 mg) was added to a solution of 2-[1-(benzylamino)cyclobutyl]propanol (6.81 g, 31.1 mmol) in EtOH (150 mL) and the mixture was stirred under H2 gas 5 kgf/cm2 at room temperature for 6 hours. The mixture was filtered, and the filtrate was concentrated in vacuo. Distillation of the residue gave the title compound as a colorless oil (2.96 g, 74%). 1H-NMR (400 MHz, CDCl3) δ 1.03 (3H, d, J=7.3 Hz), 1.63-1.74 (3H, m), 1.78-1.94 (2H, m), 2.10-2.28 (2H, m), 3.50 (1H, dd, J=11.0 and 4.3 Hz), 3.91 (1H, dd, J=11.0 and 3.1 Hz). The mixture was filtered the filtrate was concentrated in vacuo Distillation of the residue

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

Procedure: A solution of 3-oxo-3-(2,3,4,5-tetrafluorophenyl)propionate (6.13 g, 23.2 mmol), Ac2O (13.2 mL, 0.140 mol) and triethyl orthoformate (7.80 mL, 46.8 mmol) was stirred at 120° C. for 3 hours. The mixture was concentrated in vacuo and dried under high vacuum. To the mixture of the residue in anhydrous toluene (100 mL) was slowly added 2-(1-aminocyclobutyl)propanol (3.00 g, 23.2 mmol) in anhydrous toluene (40 mL) at 0° C. The mixture was stirred at room temperature for 2 hours and the solvent was removed by evaporation. Flash chromatography (AcOEt:Hexane=1:1) of the residue gave the title compound as a colorless solid (6.23 g, 67%). 1H-NMR (400 MHz, CDCl3) δ 0.95 (0.6H, t, J=7.3 Hz), 0.97 (3H, d, J=7.3 Hz), 1.09 (2.4H, t, J=7.3 Hz), 1.54 (1H, t, J=4.9 Hz), 1.85-2.15 (3H, m), 2.19-2.50 (4H, m), 3.62-3.75 (2H, m), 4.02 (0.2H, q, J=7.3 Hz), 4.07 (0.8H, q, J=7.3 Hz), 6.97-7.13 (1H, m), 8.24 (0.8H, d, J=15.3 Hz), 8.25 (0.2H, d, J=15.3 Hz), 10.03 (0.2H, d, J=14.1 Hz), 11.40 (0.8H, d, J=14.1 Hz). The mixture was concentrated in vacuo dried under high vacuum To the mixture of the residue in anhydrous toluene (100 mL) at 0° C the solvent was removed by evaporation

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

Procedure: 10% Pd—C (700 mg) was added to a solution of 2-[1-(benzylamino)cyclobutyl]propanol (6.81 g, 31.1 mmol) in EtOH (150 mL) and the mixture was stirred under H2 gas 5 kgf/cm2 at room temperature for 6 hours. The mixture was filtered, and the filtrate was concentrated in vacuo. Distillation of the residue gave the title compound as a colorless oil (2.96 g, 74%). 1H-NMR (400 MHz, CDCl3) δ1.03 (3H, d, J=7.3 Hz), 1.63-1.74 (3H, m), 1.78-1.94 (2H, m), 2.10-2.28 (2H, m), 3.50 (1H, dd, J=11.0 and 4.3 Hz), 3.91 (1H, dd, J=11.0 and 3.1 Hz). The mixture was filtered the filtrate was concentrated in vacuo Distillation of the residue

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

Procedure: A solution of 3-oxo-3-(2,3,4,5-tetrafluorophenyl)propionate (6.13 g, 23.2 mmol), Ac2O (13.2 mL, 0.140 mol) and triethyl orthoformate (7.80 mL, 46.8 mmol) was stirred at 120° C. for 3 hours. The mixture was concentrated in vacuo and dried under high vacuum. To the mixture of the residue in anhydrous toluene (100 mL) was slowly added 2-(1-aminocyclobutyl)propanol (3.00 g, 23.2 mmol) in anhydrous toluene (40 mL) at 0° C. The mixture was stirred at room temperature for 2 hours and the solvent was removed by evaporation. Flash chromatography (AcOEt:Hexane=1:1) of the residue gave the title compound as a colorless solid (6.23 g, 67%). 1H-NMR (400 MHz, CDCl3) δ 0.95 (0.6H, t, J=7.3 Hz), 0.97 (3H, d, J=7.3 Hz), 1.09 (2.4H, t, J=7.3 Hz), 1.54 (1H, t, J=4.9 Hz), 1.85-2.15 (3H, m), 2.19-2.50 (4H, m), 3.62-3.75 (2H, m), 4.02 (0.2H, q, J=7.3 Hz), 4.07 (0.8H, q, J=7.3 Hz), 6.97-7.13 (1H, m), 8.24 (0.8H, d, J=15.3 Hz), 8.25 (0.2H, d, J=15.3 Hz), 10.03 (0.2H, d, J=14.1 Hz), 11.40 (0.8H, d, J=14.1 Hz). The mixture was concentrated in vacuo dried under high vacuum To the mixture of the residue in anhydrous toluene (100 mL) at 0° C the solvent was removed by evaporation

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

Procedure: 10% Pd—C (700 mg) was added to a solution of 2-[1-(benzylamino)cyclobutyl]propanol (6.81 g, 31.1 mmol) in EtOH (150 mL) and the mixture was stirred under H2 gas 5 kgf/cm2 at room temperature for 6 hours. The mixture was filtered, and the filtrate was concentrated in vacuo. Distillation of the residue gave the title compound as a colorless oil (2.96 g, 74%). 1H-NMR (400 MHz, CDCl3) δ 1.03 (3H, d, J=7.3 Hz), 1.63-1.74 (3H, m), 1.78-1.94 (2H, m), 2.10-2.28 (2H, m), 3.50 (1H, dd, J=11.0 and 4.3 Hz), 3.91 (1H, dd, J=11.0 and 3.1 Hz). The mixture was filtered the filtrate was concentrated in vacuo Distillation of the residue