[(3-溴-4-氟苯基)甲基]-氨基甲酸叔-丁酯

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under N2, a toluene (4.70 mL)/water (0.235 mL) solution of tert-butyl 3-bromo-4-fluorobenzylcarbamate (0.300 g, 0.986 mmol) was treated with potassium phosphate tribasic (0.733 g, 3.45 mmol), cyclopropylboronic acid (0.110 g, 1.282 mmol), and tricyclohexenylphosphene (0.028 g, 0.099 mmol) in was added palladium(II) acetate (0.011 g, 0.049 mmol). The reaction was stirred at 100° C. for 3 h. The solution was diluted with water (15 mL) then extracted with ethyl acetate (2×15 mL). The organic extracts were combined, washed with brine (20 mL), then dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography (Biotage flash chromatography system; 60 g SiO2; 0-20% ethyl acetate:hexane over 900 mL) to give the title compound as a white crystalline solid (0.230 g, 88% yield). 1H NMR (500 MHz, CDCl3) δ: 6.98-7.05 (1 H, m), 6.90-6.97 (1 H, m), 6.79 (1 H, dd, J=7.02, 1.53 Hz), 4.75 (1 H, brs), 4.21 (2 H, d, J=5.49 Hz), 2.02-2.09 (1 H, m), 1.45 (9 H, s), 0.93-1.01 (2 H, m), 0.66-0.75 (2 H, m). then extracted with ethyl acetate (2×15 mL) washed with brine (20 mL) dried (MgSO4) filtered concentrated The residue was purified by flash chromatography (Biotage flash chromatography system; 60 g SiO2; 0-20% ethyl acetate:hexane over 900 mL)

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under N2, a toluene (4.70 mL)/water (0.235 mL) solution of tert-butyl 3-bromo-4-fluorobenzylcarbamate (0.300 g, 0.986 mmol) was treated with potassium phosphate tribasic (0.733 g, 3.45 mmol), cyclopropylboronic acid (0.110 g, 1.282 mmol), and tricyclohexenylphosphene (0.028 g, 0.099 mmol) in was added palladium(II) acetate (0.011 g, 0.049 mmol). The reaction was stirred at 100° C. for 3 h. The solution was diluted with water (15 mL) then extracted with ethyl acetate (2×15 mL). The organic extracts were combined, washed with brine (20 mL), then dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography (Biotage flash chromatography system; 60 g SiO2; 0-20% ethyl acetate:hexane over 900 mL) to give the title compound as a white crystalline solid (0.230 g, 88% yield). 1H NMR (500 MHz, CDCl3) δ: 6.98-7.05 (1 H, m), 6.90-6.97 (1 H, m), 6.79 (1 H, dd, J=7.02, 1.53 Hz), 4.75 (1 H, brs), 4.21 (2 H, d, J=5.49 Hz), 2.02-2.09 (1 H, m), 1.45 (9 H, s), 0.93-1.01 (2 H, m), 0.66-0.75 (2 H, m). then extracted with ethyl acetate (2×15 mL) washed with brine (20 mL) dried (MgSO4) filtered concentrated The residue was purified by flash chromatography (Biotage flash chromatography system; 60 g SiO2; 0-20% ethyl acetate:hexane over 900 mL)

反应条件: temp:8.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To the solution of 1,1-dimethylethyl [(3-bromo-4-fluorophenyl)methyl]carbamate (0.755 g, 2.48 mmol) in THF (1 mL) was added BH3.THF (12.5 mL, 1.0 M in THF). The mixture was heated in a microwave machine at about 8° C. for about 30 mins twice. The reaction was then quenched with HCl (10 mL, 1 N) slowly, stirred for 2 h at room temperature, basified with NaHCO3 to pH ˜9, and extracted with EtOAc (50+20 mL). The organic layer was washed with brine, dried over Na2SO4, filtered, concentrated to afford 0.52 g (96%) of the title compound. LC-MS m/z 218 (M+H)+. The reaction was then quenched with HCl (10 mL, 1 N) slowly extracted with EtOAc (50+20 mL) The organic layer was washed with brine dried over Na2SO4 filtered concentrated

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1,1-dimethylethyl [(3-bromo-4-fluorophenyl)methyl]carbamate (0.755 g, 2.48 mmol) in THF (1 mL) was added BH3.THF (12.5 mL, 1.0 M in THF). The mixture was heated with a microwave at 80° C. for 30 min twice. The reaction was then quenched with HCl (10 mL, 1 N) slowly, after which the mixture was stirred for 2 h at room temperature, basified with NaHCO3 to pH ˜9, and extracted with EtOAc (50+20 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered, concentrated to afford the title compound 0.52 g (96%). LC-MS m/z 218 (M+H)+. The reaction was then quenched with HCl (10 mL, 1 N) slowly extracted with EtOAc (50+20 mL) The combined organic phases were washed with brine dried over Na2SO4 filtered concentrated

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1,1-dimethylethyl [(3-bromo-4-fluorophenyl)methyl]carbamate (0.755 g, 2.48 mmol) in THF (1 mL) was added BH3.THF (12.5 mL, 1.0 M in THF). The mixture was heated with a microwave at 80° C. for 30 min twice. The reaction was then quenched with HCl (10 mL, 1 N) slowly, after which the mixture was stirred for 2 h at room temperature, basified with NaHCO3 to pH ˜9, and extracted with EtOAc (50+20 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered, concentrated to afford the title compound 0.52 g (96%). LC-MS m/z 218 (M+H)+. The reaction was then quenched with HCl (10 mL, 1 N) slowly extracted with EtOAc (50+20 mL) The combined organic phases were washed with brine dried over Na2SO4 filtered concentrated

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of tert-butoxy-N-[(3-bromo-4-fluorophenyl)methyl]carboxamide (0.6 g, 2.0 mmol, Step A), CuI (38 mg, 0.2 mmol), PdCl2(PPh3)2 (72 mg, 0.1 mmol), propargyl alcohol (0.35 mL, 6.0 mmol) and TEA (12 mL) was heated at 100° C. for 5 h. The resulting mixture was filtered, and the filtrate was concentrated. The residue was purified by SiO2 chromatography to give the title compound. MS (ES+): 297 (M+NH4)+. Calc'd C15H22FN2O3-297.34. The resulting mixture was filtered the filtrate was concentrated The residue was purified by SiO2 chromatography

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

实验步骤: To a solution of 3-bromo-4-fluorobenzylamine (10 g, 41 mmol) and TEA (14 mL, 104 mmol) in CH2Cl2 was added BOC2O (9.1 g, 41 mmol). The resulting solution was stirred for 16 h at RT, then diluted with aq. 1 N NaOH and CH2Cl2. The organic layer was separated, washed with brine, dried over Na2SO4, and concentrated to give (tert-butoxy)-N-[(3-bromo-4-fluorophenyl)methyl]carboxamide. The organic layer was separated washed with brine dried over Na2SO4 concentrated

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

实验步骤: To a solution of 3-bromo-4-fluorobenzylamine (10 g, 41 mmol) and TEA (14 mL, 104 mmol) in CH2Cl2 was added BOC2O (9.1 g, 41 mmol). The resulting solution was stirred for 16 h at RT, then diluted with aq. 1 N NaOH and CH2Cl2. The organic layer was separated, washed with brine, dried over Na2SO4, and concentrated to give (tert-butoxy)-N-[(3-bromo-4-fluorophenyl)methyl]carboxamide. The organic layer was separated washed with brine dried over Na2SO4 concentrated

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

实验步骤: To a solution of 3-bromo-4-fluorobenzylamine (10 g, 41 mmol) and TEA (14 mL, 104 mmol) in CH2Cl2 was added BOC2O (9.1 g, 41 mmol). The resulting solution was stirred for 16 h at RT, then diluted with aq. 1 N NaOH and CH2Cl2. The organic layer was separated, washed with brine, dried over Na2SO4, and concentrated to give (tert-butoxy)-N-[(3-bromo-4-fluorophenyl)methyl]carboxamide. The organic layer was separated washed with brine dried over Na2SO4 concentrated

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

实验步骤: To a solution of 3-bromo-4-fluorobenzylamine hydrochloride (10 g, 42 mmol) and TEA (10.5 g, 103 mmol) in 200 mL of CH2Cl2 was added BOC2O (9.1 g, 42 mmol) at RT. The resulting solution was stirred for 16 h. The solution was diluted with aq. 1 N NaOH and CH2Cl2. The organic layer was washed with brine, dried over Na2SO4, and concentrated to give N-Boc-(3-bromo-4-fluoro-benzyl)amine. MS (ES+): 305 (M+H)+; (ES−): 303 (M−H). Calc'd C12H15BrFNO2-304.16. The organic layer was washed with brine dried over Na2SO4 concentrated