乙基 2-(4-乙基苯基)乙酸甲酯

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

实验步骤: KOtBu (11.8 g) is added to a flask charged with a stir bar and dry NMP (40 mL) and chilled to −10° C. under argon atmosphere. A solution of ethyl (4-ethyl-phenyl)-acetate (10.1 g) and 1-bromo-4-cyano-3,5-difluoro-benzene (11.5 g) in NMP (40 mL) is added at such a rate that the reaction temperature maintains below 10° C. After stirring for 1 hour at room temperature, methanol (50 mL) and 1 M aqueous sodium hydroxide solution (39 mL) are added and the resulting mixture is stirred overnight at 100° C. Then, 4 M aqueous hydrochloric acid (100 mL) is added and the mixture is stirred for another h at 100° C. The methanol fraction is evaporated, water (200 mL) is added to the residue and the resulting mixture is extracted with ethyl acetate. The combined organic extracts are washed twice with water, twice with brine and dried (MgSO4). The solvent is evaporated and the residue is washed with methanol. The insoluble residue is separated by filtration and dried to give the white product. charged with a stir bar maintains below 10° C the resulting mixture is stirred overnight at 100° C the mixture is stirred for another h at 100° C The methanol fraction is evaporated water (200 mL) is added to the residue the resulting mixture is extracted with ethyl acetate The combined organic extracts are washed twice with water, twice with brine dried (MgSO4) The solvent is evaporated the residue is washed with methanol The insoluble residue is separated by filtration dried to give the white product

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

实验步骤: KOtBu (11.8 g) is added to a flask charged with a stir bar and dry NMP (40 mL) and chilled to −10° C. under argon atmosphere. A solution of ethyl (4-ethyl-phenyl)-acetate (10.1 g) and 1-bromo-4-cyano-3,5-difluoro-benzene (11.5 g) in NMP (40 mL) is added at such a rate that the reaction temperature maintains below 10° C. After stirring for 1 hour at room temperature, methanol (50 mL) and 1 M aqueous sodium hydroxide solution (39 mL) are added and the resulting mixture is stirred overnight at 100° C. Then, 4 M aqueous hydrochloric acid (100 mL) is added and the mixture is stirred for another h at 100° C. The methanol fraction is evaporated, water (200 mL) is added to the residue and the resulting mixture is extracted with ethyl acetate. The combined organic extracts are washed twice with water, twice with brine and dried (MgSO4). The solvent is evaporated and the residue is washed with methanol. The insoluble residue is separated by filtration and dried to give the white product. charged with a stir bar maintains below 10° C the resulting mixture is stirred overnight at 100° C the mixture is stirred for another h at 100° C The methanol fraction is evaporated water (200 mL) is added to the residue the resulting mixture is extracted with ethyl acetate The combined organic extracts are washed twice with water, twice with brine dried (MgSO4) The solvent is evaporated the residue is washed with methanol The insoluble residue is separated by filtration dried to give the white product

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: KOtBu (6.7 g) is added to a flask charged with a stir bar and dry NMP (30 mL) and chilled to −10° C. under argon atmosphere. A solution of ethyl (4-ethyl-phenyl)-acetate (5.6 g) and 1-bromo-4-cyano-3,5-difluoro-benzene (6.4 g) in NMP (20 mL) is added at such a rate that the solution temperature maintains below 10° C. After stirring for 1 hour at 10° C., the solution is neutralized with 1 M aqueous hydrochloric acid and extracted with ethyl acetate. The combined extracts are dried (Na2SO4) and the solvent is evaporated. The residue is dissolved in THF (20 mL) and treated with 1M aqueous NaOH solution (80 mL). After stirring overnight at room temperature, the solution is acidified with 4 M HCl solution and extracted with ethyl acetate. The organic extracts are combined and dried (Na2SO4) and the solvent is evaporated. The residue is dissolved in DMF (25 mL) and K2CO3 (5.5 g) is added. The resulting mixture is stirred at 100° C. for 1 h. After cooling to room temperature, the mixture is neutralized with 1 M aqueous hydrochloric acid and the resultant mixture is extracted with ethyl acetate. The combined organic extracts are dried (MgSO4) and the solvent is evaporated. The residue is purified by chromatography on silica gel (cyclohexane/ethyl acetate 1:0->1:1). charged with a stir bar maintains below 10° C extracted with ethyl acetate The combined extracts are dried (Na2SO4) the solvent is evaporated The residue is dissolved in THF (20 mL) treated with 1M aqueous NaOH solution (80 mL) After stirring overnight at room temperature extracted with ethyl acetate dried (Na2SO4) the solvent is evaporated The residue is dissolved in DMF (25 mL) K2CO3 (5.5 g) is added The resulting mixture is stirred at 100° C. for 1 h After cooling to room temperature the resultant mixture is extracted with ethyl acetate The combined organic extracts are dried (MgSO4) the solvent is evaporated The residue is purified by chromatography on silica gel (cyclohexane/ethyl acetate 1:0->1:1)

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

实验步骤: KOtBu (11.8 g) is added to a flask charged with a stir bar and dry NMP (40 mL) and chilled to −10° C. under argon atmosphere. A solution of ethyl (4-ethyl-phenyl)-acetate (10.1 g) and 1-bromo-4-cyano-3,5-difluoro-benzene (11.5 g) in NMP (40 mL) is added at such a rate that the reaction temperature maintains below 10° C. After stirring for 1 hour at room temperature, methanol (50 mL) and 1 M aqueous sodium hydroxide solution (39 mL) are added and the resulting mixture is stirred overnight at 100° C. Then, 4 M aqueous hydrochloric acid (100 mL) is added and the mixture is stirred for another h at 100° C. The methanol fraction is evaporated, water (200 mL) is added to the residue and the resulting mixture is extracted with ethyl acetate. The combined organic extracts are washed twice with water, twice with brine and dried (MgSO4). The solvent is evaporated and the residue is washed with methanol. The insoluble residue is separated by filtration and dried to give the white product. charged with a stir bar maintains below 10° C the resulting mixture is stirred overnight at 100° C the mixture is stirred for another h at 100° C The methanol fraction is evaporated water (200 mL) is added to the residue the resulting mixture is extracted with ethyl acetate The combined organic extracts are washed twice with water, twice with brine dried (MgSO4) The solvent is evaporated the residue is washed with methanol The insoluble residue is separated by filtration dried to give the white product

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

实验步骤: KOtBu (11.8 g) is added to a flask charged with a stir bar and dry NMP (40 mL) and chilled to −10° C. under argon atmosphere. A solution of ethyl (4-ethyl-phenyl)-acetate (10.1 g) and 1-bromo-4-cyano-3,5-difluoro-benzene (11.5 g) in NMP (40 mL) is added at such a rate that the reaction temperature maintains below 10° C. After stirring for 1 hour at room temperature, methanol (50 mL) and 1 M aqueous sodium hydroxide solution (39 mL) are added and the resulting mixture is stirred overnight at 100° C. Then, 4 M aqueous hydrochloric acid (100 mL) is added and the mixture is stirred for another h at 100° C. The methanol fraction is evaporated, water (200 mL) is added to the residue and the resulting mixture is extracted with ethyl acetate. The combined organic extracts are washed twice with water, twice with brine and dried (MgSO4). The solvent is evaporated and the residue is washed with methanol. The insoluble residue is separated by filtration and dried to give the white product. charged with a stir bar maintains below 10° C the resulting mixture is stirred overnight at 100° C the mixture is stirred for another h at 100° C The methanol fraction is evaporated water (200 mL) is added to the residue the resulting mixture is extracted with ethyl acetate The combined organic extracts are washed twice with water, twice with brine dried (MgSO4) The solvent is evaporated the residue is washed with methanol The insoluble residue is separated by filtration dried to give the white product