1-N-Benzyl-5-fluorobenzene-1,2-diamine

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N2-Benzyl-4-fluoro-benzene-1,2-diamine (1.2 g, 5.55 mmol) was dissolved in DCM (20 mL) and (S)-2-tert-butoxycarbonylaminopropionic acid (1.14 g, 6.0 mmol) and HOAt (0.82 g, 6.0 mmol) added. The reaction mixture was cooled to 0° C. and N-(3-dimethylaminopropyl)-N′ ethylcarbodiimide (1.15 g, 6.0 mmol) added. The resultant dark brown mixture was stirred at 0° C. for 1 h. The mixture was allowed to reach RT and was diluted with DCM (20 mL) and washed with 10% aqueous citric acid. The organic fraction was washed with brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, gradient 0-50% EtOAc in cyclohexane) to afford the title compound as a dark yellow gum, which solidified on standing (1.7 g, 79%). LCMS (Method B): RT 3.67 min [M+H]+ 388.1 to reach RT washed with 10% aqueous citric acid The organic fraction was washed with brine (20 mL) dried (MgSO4) filtered concentrated in vacuo The residue was purified by column chromatography (silica gel, gradient 0-50% EtOAc in cyclohexane)

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of benzyl-(5-fluoro-2-nitrophenyl)amine (3.8 g, 15.2 mmol), iron powder (3.42 g, 60.8 mmol) and ammonium chloride (4.7 g, 91.2 mmol) in methanol (40 mL) and water (10 mL) was heated to 90° C. for 2 h, under an atmosphere of nitrogen. The resultant mixture was diluted with methanol (20 mL) and filtered through Celite®. The Celite® was washed with DCM, methanol and EtOAc (4×) and the filtrate concentrated in vacuo. The residue was partitioned between water (25 mL) and EtOAc (40 mL) and the aqueous layer was extracted with EtOAc (2×30 mL). The combined organic fractions were washed with brine (25 mL), dried (MgSO4), filtered and concentrated in vacuo to afford the title compound as a dark brown gum (2.17 g, 66%). The crude material was used without purification in the next step. 1H NMR (CDCl3, 400 MHz): δ 7.41-7.25 (5H, m), 6.67-6.59 (1H, m), 6.40-6.28 (2H, m), 4.28 (2H, s) filtered through Celite® The Celite® was washed with DCM, methanol and EtOAc (4×) the filtrate concentrated in vacuo The residue was partitioned between water (25 mL) and EtOAc (40 mL) the aqueous layer was extracted with EtOAc (2×30 mL) The combined organic fractions were washed with brine (25 mL) dried (MgSO4) filtered concentrated in vacuo

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of benzyl-(5-fluoro-2-nitrophenyl)amine (3.8 g, 15.2 mmol), iron powder (3.42 g, 60.8 mmol) and ammonium chloride (4.7 g, 91.2 mmol) in methanol (40 mL) and water (10 mL) was heated to 90° C. for 2 h, under an atmosphere of nitrogen. The resultant mixture was diluted with methanol (20 mL) and filtered through Celite®. The Celite® was washed with DCM, methanol and EtOAc (4×) and the filtrate concentrated in vacuo. The residue was partitioned between water (25 mL) and EtOAc (40 mL) and the aqueous layer was extracted with EtOAc (2×30 mL). The combined organic fractions were washed with brine (25 mL), dried (MgSO4), filtered and concentrated in vacuo to afford the title compound as a dark brown gum (2.17 g, 66%). The crude material was used without purification in the next step. 1H NMR (CDCl3, 400 MHz): δ 7.41-7.25 (5H, m), 6.67-6.59 (1H, m), 6.40-6.28 (2H, m), 4.28 (2H, s) filtered through Celite® The Celite® was washed with DCM, methanol and EtOAc (4×) the filtrate concentrated in vacuo The residue was partitioned between water (25 mL) and EtOAc (40 mL) the aqueous layer was extracted with EtOAc (2×30 mL) The combined organic fractions were washed with brine (25 mL) dried (MgSO4) filtered concentrated in vacuo

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N2-Benzyl-4-fluoro-benzene-1,2-diamine (1.2 g, 5.55 mmol) was dissolved in DCM (20 mL) and (S)-2-tert-butoxycarbonylaminopropionic acid (1.14 g, 6.0 mmol) and HOAt (0.82 g, 6.0 mmol) added. The reaction mixture was cooled to 0° C. and N-(3-dimethylaminopropyl)-N′ ethylcarbodiimide (1.15 g, 6.0 mmol) added. The resultant dark brown mixture was stirred at 0° C. for 1 h. The mixture was allowed to reach RT and was diluted with DCM (20 mL) and washed with 10% aqueous citric acid. The organic fraction was washed with brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, gradient 0-50% EtOAc in cyclohexane) to afford the title compound as a dark yellow gum, which solidified on standing (1.7 g, 79%). LCMS (Method B): RT 3.67 min [M+H]+ 388.1 to reach RT washed with 10% aqueous citric acid The organic fraction was washed with brine (20 mL) dried (MgSO4) filtered concentrated in vacuo The residue was purified by column chromatography (silica gel, gradient 0-50% EtOAc in cyclohexane)

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of benzyl-(5-fluoro-2-nitrophenyl)amine (3.8 g, 15.2 mmol), iron powder (3.42 g, 60.8 mmol) and ammonium chloride (4.7 g, 91.2 mmol) in methanol (40 mL) and water (10 mL) was heated to 90° C. for 2 h, under an atmosphere of nitrogen. The resultant mixture was diluted with methanol (20 mL) and filtered through Celite®. The Celite® was washed with DCM, methanol and EtOAc (4×) and the filtrate concentrated in vacuo. The residue was partitioned between water (25 mL) and EtOAc (40 mL) and the aqueous layer was extracted with EtOAc (2×30 mL). The combined organic fractions were washed with brine (25 mL), dried (MgSO4), filtered and concentrated in vacuo to afford the title compound as a dark brown gum (2.17 g, 66%). The crude material was used without purification in the next step. 1H NMR (CDCl3, 400 MHz): δ 7.41-7.25 (5H, m), 6.67-6.59 (1H, m), 6.40-6.28 (2H, m), 4.28 (2H, s) filtered through Celite® The Celite® was washed with DCM, methanol and EtOAc (4×) the filtrate concentrated in vacuo The residue was partitioned between water (25 mL) and EtOAc (40 mL) the aqueous layer was extracted with EtOAc (2×30 mL) The combined organic fractions were washed with brine (25 mL) dried (MgSO4) filtered concentrated in vacuo

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N2-Benzyl-4-fluoro-benzene-1,2-diamine (1.2 g, 5.55 mmol) was dissolved in DCM (20 mL) and (S)-2-tert-butoxycarbonylaminopropionic acid (1.14 g, 6.0 mmol) and HOAt (0.82 g, 6.0 mmol) added. The reaction mixture was cooled to 0° C. and N-(3-dimethylaminopropyl)-N′ ethylcarbodiimide (1.15 g, 6.0 mmol) added. The resultant dark brown mixture was stirred at 0° C. for 1 h. The mixture was allowed to reach RT and was diluted with DCM (20 mL) and washed with 10% aqueous citric acid. The organic fraction was washed with brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, gradient 0-50% EtOAc in cyclohexane) to afford the title compound as a dark yellow gum, which solidified on standing (1.7 g, 79%). LCMS (Method B): RT 3.67 min [M+H]+ 388.1 to reach RT washed with 10% aqueous citric acid The organic fraction was washed with brine (20 mL) dried (MgSO4) filtered concentrated in vacuo The residue was purified by column chromatography (silica gel, gradient 0-50% EtOAc in cyclohexane)

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of benzyl-(5-fluoro-2-nitrophenyl)amine (3.8 g, 15.2 mmol), iron powder (3.42 g, 60.8 mmol) and ammonium chloride (4.7 g, 91.2 mmol) in methanol (40 mL) and water (10 mL) was heated to 90° C. for 2 h, under an atmosphere of nitrogen. The resultant mixture was diluted with methanol (20 mL) and filtered through Celite®. The Celite® was washed with DCM, methanol and EtOAc (4×) and the filtrate concentrated in vacuo. The residue was partitioned between water (25 mL) and EtOAc (40 mL) and the aqueous layer was extracted with EtOAc (2×30 mL). The combined organic fractions were washed with brine (25 mL), dried (MgSO4), filtered and concentrated in vacuo to afford the title compound as a dark brown gum (2.17 g, 66%). The crude material was used without purification in the next step. 1H NMR (CDCl3, 400 MHz): δ 7.41-7.25 (5H, m), 6.67-6.59 (1H, m), 6.40-6.28 (2H, m), 4.28 (2H, s) filtered through Celite® The Celite® was washed with DCM, methanol and EtOAc (4×) the filtrate concentrated in vacuo The residue was partitioned between water (25 mL) and EtOAc (40 mL) the aqueous layer was extracted with EtOAc (2×30 mL) The combined organic fractions were washed with brine (25 mL) dried (MgSO4) filtered concentrated in vacuo