4-溴-2-氟-6-苯基甲氧基苯胺

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of 2.6 g (8.78 mmol) of 2-benzyloxy-4-bromo-6-fluoroaniline and 3.03 g (21.96 mmol) of potassium carbonate in 20 mL DMF in an oil bath at 60° C. is added 1.48 g (9.67 mmole) of methyl bromoacetate. The mixture is stirred at 60° C. for 2 h. HPLC analysis indicated that the reaction is 38% complete. Additional methyl bromoacetate equal to the molar amount of unreacted starting material is added and the mixture is stirred at 60° C. for 2 h. This process is repeated until the starting material is nearly consumed. The mixture is allowed to cool then is poured into water. The mixture is extracted with ethyl acetate and the organic phase is washed 3× with water. The organic solution is dried over sodium sulfate and the solvent is removed under reduced pressure. The residual dark oil is purified by flash chromatography using methylene chloride to elute the product as a dark oil. This is used directly in the next step. is added the mixture is stirred at 60° C. for 2 h is nearly consumed to cool then is poured into water The mixture is extracted with ethyl acetate the organic phase is washed 3× with water The organic solution is dried over sodium sulfate the solvent is removed under reduced pressure The residual dark oil is purified by flash chromatography to elute the product as a dark oil

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

实验步骤: To a solution of 2-benzyloxy-6-fluorophenylamine (7.29 g, 33.6 mmol) in MeOH/HOAc (3:1 v/v, 30 mL) at 0° C. is added bromine (2.2 mL, 47 mmol) in MeOH/HOAc (3:1 v/v, 4 mL) drop wise. After it is stirred for 4 h, the reaction is completed by LC/MS. The reaction mixture is concentrated, and the residue is stirred with EtOAc and 1N NaOH to dissolve solid. Additional base is added to make the aqueous alkaline, and then EtOAc layer is separated. The organic phase is washed with brine, dried and filtered. The concentrated residue is purified to give the title compound: 1H NMR (CDCl3) 7.39 (m, 5H), 6.86 (dd, 1H, J=9.8, 2.0 Hz), 6.81 (m, 1H), 5.05 (s, 2H), 3.77 (br s, 2H); MS (M+H)+=296, 298. The reaction mixture is concentrated the residue is stirred with EtOAc and 1N NaOH to dissolve solid Additional base is added EtOAc layer is separated The organic phase is washed with brine dried filtered The concentrated residue is purified

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

实验步骤: To a solution of 2-benzyloxy-6-fluorophenylamine (7.29 g, 33.6 mmol) in MeOH/HOAc (3:1 v/v, 30 mL) at 0° C. is added bromine (2.2 mL, 47 mmol) in MeOH/HOAc (3:1 v/v, 4 mL) drop wise. After it is stirred for 4 h, the reaction is completed by LC/MS. The reaction mixture is concentrated, and the residue is stirred with EtOAc and 1N NaOH to dissolve solid. Additional base is added to make the aqueous alkaline, and then EtOAc layer is separated. The organic phase is washed with brine, dried and filtered. The concentrated residue is purified to give the title compound: 1H NMR (CDCl3) 7.39 (m, 5H), 6.86 (dd, 1H, J=9.8, 2.0 Hz), 6.81 (m, 1H), 5.05 (s, 2H), 3.77 (br s, 2H); MS (M+H)+=296, 298. The reaction mixture is concentrated the residue is stirred with EtOAc and 1N NaOH to dissolve solid Additional base is added EtOAc layer is separated The organic phase is washed with brine dried filtered The concentrated residue is purified

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of 2.6 g (8.78 mmol) of 2-benzyloxy-4-bromo-6-fluoroaniline and 3.03 g (21.96 mmol) of potassium carbonate in 20 mL DMF in an oil bath at 60° C. is added 1.48 g (9.67 mmole) of methyl bromoacetate. The mixture is stirred at 60° C. for 2 h. HPLC analysis indicated that the reaction is 38% complete. Additional methyl bromoacetate equal to the molar amount of unreacted starting material is added and the mixture is stirred at 60° C. for 2 h. This process is repeated until the starting material is nearly consumed. The mixture is allowed to cool then is poured into water. The mixture is extracted with ethyl acetate and the organic phase is washed 3× with water. The organic solution is dried over sodium sulfate and the solvent is removed under reduced pressure. The residual dark oil is purified by flash chromatography using methylene chloride to elute the product as a dark oil. This is used directly in the next step. is added the mixture is stirred at 60° C. for 2 h is nearly consumed to cool then is poured into water The mixture is extracted with ethyl acetate the organic phase is washed 3× with water The organic solution is dried over sodium sulfate the solvent is removed under reduced pressure The residual dark oil is purified by flash chromatography to elute the product as a dark oil

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

实验步骤: To a solution of 2-benzyloxy-6-fluorophenylamine (7.29 g, 33.6 mmol) in MeOH/HOAc (3:1 v/v, 30 mL) at 0° C. is added bromine (2.2 mL, 47 mmol) in MeOH/HOAc (3:1 v/v, 4 mL) drop wise. After it is stirred for 4 h, the reaction is completed by LC/MS. The reaction mixture is concentrated, and the residue is stirred with EtOAc and 1N NaOH to dissolve solid. Additional base is added to make the aqueous alkaline, and then EtOAc layer is separated. The organic phase is washed with brine, dried and filtered. The concentrated residue is purified to give the title compound: 1H NMR (CDCl3) 7.39 (m, 5H), 6.86 (dd, 1H, J=9.8, 2.0 Hz), 6.81 (m, 1H), 5.05 (s, 2H), 3.77 (br s, 2H); MS (M+H)+=296, 298. The reaction mixture is concentrated the residue is stirred with EtOAc and 1N NaOH to dissolve solid Additional base is added EtOAc layer is separated The organic phase is washed with brine dried filtered The concentrated residue is purified

反应条件: temp:0.00; pressure:0.00; stir: