2-氰基-2-(二氢-2H-吡喃4(3H)-亚芴基)乙酸甲酯

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

实验步骤: A round bottom flask was equipped with a condenser, addition funnel and rubber septum with nitrogen inlet was charged with a solution of p-fluorophenylmagnesium bromide (2.0 M in diethyl ether, 1.99 ml, 3.97 mmol) and CuI (63 mg, 0.331 mmol) in 10 ml dry diethyl ether (10 ml). Methyl 2-cyano-2-(oxan-4-ylidene)acetate (600 mg, 3.31 mmol) in diethyl ether (10 ml) was added drop-wise over 30 min while cooling the reaction flask in an ice bath. The mixture was then stirred for 3 h. The reaction mixture was poured into a 50 g ice/1 N HCl (25 ml) mixture. The product was extracted with Et2O (3×50 ml), washed with brine (50 ml), dried (NA2SO4) and concentrated. Purified by normal phase SiO2 chromatography (7% to 60% EtOAc/hexanes) to give methyl 2-cyano-2-[4-(4-fluorophenyl)oxan-4-yl]acetate as a white solid (730 mg, 80%, m/z: 277.1 [M+Na]+ observed). A round bottom flask was equipped with a condenser, addition funnel while cooling the reaction flask in an ice bath The product was extracted with Et2O (3×50 ml) washed with brine (50 ml) dried (NA2SO4) concentrated Purified by normal phase SiO2 chromatography (7% to 60% EtOAc/hexanes)

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

实验步骤: A 50 ml round-bottom flask equipped with a Dean-Stark distillation setup and condenser was charged with tetrahydro-4H-pyran-4-one (4.61 ml, 50 mmol), methyl cyanoacetate (5.3 ml, 60 mmol), ammonium acetate (1 g, 13 mmol), acetic acid (0.57 ml, 10 mmol) and benzene (30 ml). The mixture was refluxed until no more water collected in the Dean-Stark (2 hours), cooled, benzene (30 ml) added and the organic layer washed with water (50 ml). The aqueous layer was extracted with CH2Cl2 (3×50 ml). The combined organic phase was washed with sat. NaHCO3 (100 ml), brine (100 ml) dried (MgSO4), filtered and concentrated. Purified by normal phase SiO2 chromatography (10 to 60% EtOAc/hexanes) to afford methyl 2-cyano-2-(oxan-4-ylidene)acetate as a colorless oil (6.30 g, 70%, m/z: 181.1 [M+H]+ observed). A 50 ml round-bottom flask equipped with a Dean-Stark distillation setup and condenser collected in the Dean-Stark (2 hours) cooled benzene (30 ml) added the organic layer washed with water (50 ml) The aqueous layer was extracted with CH2Cl2 (3×50 ml) The combined organic phase was washed with sat. NaHCO3 (100 ml), brine (100 ml) dried (MgSO4) filtered concentrated Purified by normal phase SiO2 chromatography (10 to 60% EtOAc/hexanes)

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

实验步骤: A 50 ml round-bottom flask equipped with a Dean-Stark distillation setup and condenser was charged with tetrahydro-4H-pyran-4-one (4.61 ml, 50 mmol), methyl cyanoacetate (5.3 ml, 60 mmol), ammonium acetate (1 g, 13 mmol), acetic acid (0.57 ml, 10 mmol) and benzene (30 ml). The mixture was refluxed until no more water collected in the Dean-Stark (2 hours), cooled, benzene (30 ml) added and the organic layer washed with water (50 ml). The aqueous layer was extracted with CH2Cl2 (3×50 ml). The combined organic phase was washed with sat. NaHCO3 (100 ml), brine (100 ml) dried (MgSO4), filtered and concentrated. Purified by normal phase SiO2 chromatography (10 to 60% EtOAc/hexanes) to afford methyl 2-cyano-2-(oxan-4-ylidene)acetate as a colorless oil (6.30 g, 70%, m/z: 181.1 [M+H]+ observed). A 50 ml round-bottom flask equipped with a Dean-Stark distillation setup and condenser collected in the Dean-Stark (2 hours) cooled benzene (30 ml) added the organic layer washed with water (50 ml) The aqueous layer was extracted with CH2Cl2 (3×50 ml) The combined organic phase was washed with sat. NaHCO3 (100 ml), brine (100 ml) dried (MgSO4) filtered concentrated Purified by normal phase SiO2 chromatography (10 to 60% EtOAc/hexanes)

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

实验步骤: A round bottom flask was equipped with a condenser, addition funnel and rubber septum with nitrogen inlet was charged with a solution of p-fluorophenylmagnesium bromide (2.0 M in diethyl ether, 1.99 ml, 3.97 mmol) and CuI (63 mg, 0.331 mmol) in 10 ml dry diethyl ether (10 ml). Methyl 2-cyano-2-(oxan-4-ylidene)acetate (600 mg, 3.31 mmol) in diethyl ether (10 ml) was added drop-wise over 30 min while cooling the reaction flask in an ice bath. The mixture was then stirred for 3 h. The reaction mixture was poured into a 50 g ice/1 N HCl (25 ml) mixture. The product was extracted with Et2O (3×50 ml), washed with brine (50 ml), dried (NA2SO4) and concentrated. Purified by normal phase SiO2 chromatography (7% to 60% EtOAc/hexanes) to give methyl 2-cyano-2-[4-(4-fluorophenyl)oxan-4-yl]acetate as a white solid (730 mg, 80%, m/z: 277.1 [M+Na]+ observed). A round bottom flask was equipped with a condenser, addition funnel while cooling the reaction flask in an ice bath The product was extracted with Et2O (3×50 ml) washed with brine (50 ml) dried (NA2SO4) concentrated Purified by normal phase SiO2 chromatography (7% to 60% EtOAc/hexanes)

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

实验步骤: A 50 ml round-bottom flask equipped with a Dean-Stark distillation setup and condenser was charged with tetrahydro-4H-pyran-4-one (4.61 ml, 50 mmol), methyl cyanoacetate (5.3 ml, 60 mmol), ammonium acetate (1 g, 13 mmol), acetic acid (0.57 ml, 10 mmol) and benzene (30 ml). The mixture was refluxed until no more water collected in the Dean-Stark (2 hours), cooled, benzene (30 ml) added and the organic layer washed with water (50 ml). The aqueous layer was extracted with CH2Cl2 (3×50 ml). The combined organic phase was washed with sat. NaHCO3 (100 ml), brine (100 ml) dried (MgSO4), filtered and concentrated. Purified by normal phase SiO2 chromatography (10 to 60% EtOAc/hexanes) to afford methyl 2-cyano-2-(oxan-4-ylidene)acetate as a colorless oil (6.30 g, 70%, m/z: 181.1 [M+H]+ observed). A 50 ml round-bottom flask equipped with a Dean-Stark distillation setup and condenser collected in the Dean-Stark (2 hours) cooled benzene (30 ml) added the organic layer washed with water (50 ml) The aqueous layer was extracted with CH2Cl2 (3×50 ml) The combined organic phase was washed with sat. NaHCO3 (100 ml), brine (100 ml) dried (MgSO4) filtered concentrated Purified by normal phase SiO2 chromatography (10 to 60% EtOAc/hexanes)

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

实验步骤: A round bottom flask was equipped with a condenser, addition funnel and rubber septum with nitrogen inlet was charged with a solution of p-fluorophenylmagnesium bromide (2.0 M in diethyl ether, 1.99 ml, 3.97 mmol) and CuI (63 mg, 0.331 mmol) in 10 ml dry diethyl ether (10 ml). Methyl 2-cyano-2-(oxan-4-ylidene)acetate (600 mg, 3.31 mmol) in diethyl ether (10 ml) was added drop-wise over 30 min while cooling the reaction flask in an ice bath. The mixture was then stirred for 3 h. The reaction mixture was poured into a 50 g ice/1 N HCl (25 ml) mixture. The product was extracted with Et2O (3×50 ml), washed with brine (50 ml), dried (NA2SO4) and concentrated. Purified by normal phase SiO2 chromatography (7% to 60% EtOAc/hexanes) to give methyl 2-cyano-2-[4-(4-fluorophenyl)oxan-4-yl]acetate as a white solid (730 mg, 80%, m/z: 277.1 [M+Na]+ observed). A round bottom flask was equipped with a condenser, addition funnel while cooling the reaction flask in an ice bath The product was extracted with Et2O (3×50 ml) washed with brine (50 ml) dried (NA2SO4) concentrated Purified by normal phase SiO2 chromatography (7% to 60% EtOAc/hexanes)

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

实验步骤: A 50 ml round-bottom flask equipped with a Dean-Stark distillation setup and condenser was charged with tetrahydro-4H-pyran-4-one (4.61 ml, 50 mmol), methyl cyanoacetate (5.3 ml, 60 mmol), ammonium acetate (1 g, 13 mmol), acetic acid (0.57 ml, 10 mmol) and benzene (30 ml). The mixture was refluxed until no more water collected in the Dean-Stark (2 hours), cooled, benzene (30 ml) added and the organic layer washed with water (50 ml). The aqueous layer was extracted with CH2Cl2 (3×50 ml). The combined organic phase was washed with sat. NaHCO3 (100 ml), brine (100 ml) dried (MgSO4), filtered and concentrated. Purified by normal phase SiO2 chromatography (10 to 60% EtOAc/hexanes) to afford methyl 2-cyano-2-(oxan-4-ylidene)acetate as a colorless oil (6.30 g, 70%, m/z: 181.1 [M+H]+ observed). A 50 ml round-bottom flask equipped with a Dean-Stark distillation setup and condenser collected in the Dean-Stark (2 hours) cooled benzene (30 ml) added the organic layer washed with water (50 ml) The aqueous layer was extracted with CH2Cl2 (3×50 ml) The combined organic phase was washed with sat. NaHCO3 (100 ml), brine (100 ml) dried (MgSO4) filtered concentrated Purified by normal phase SiO2 chromatography (10 to 60% EtOAc/hexanes)

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

实验步骤: A round bottom flask was equipped with a condenser, addition funnel and rubber septum with nitrogen inlet was charged with a solution of p-fluorophenylmagnesium bromide (2.0 M in diethyl ether, 1.99 ml, 3.97 mmol) and CuI (63 mg, 0.331 mmol) in 10 ml dry diethyl ether (10 ml). Methyl 2-cyano-2-(oxan-4-ylidene)acetate (600 mg, 3.31 mmol) in diethyl ether (10 ml) was added drop-wise over 30 min while cooling the reaction flask in an ice bath. The mixture was then stirred for 3 h. The reaction mixture was poured into a 50 g ice/1 N HCl (25 ml) mixture. The product was extracted with Et2O (3×50 ml), washed with brine (50 ml), dried (NA2SO4) and concentrated. Purified by normal phase SiO2 chromatography (7% to 60% EtOAc/hexanes) to give methyl 2-cyano-2-[4-(4-fluorophenyl)oxan-4-yl]acetate as a white solid (730 mg, 80%, m/z: 277.1 [M+Na]+ observed). A round bottom flask was equipped with a condenser, addition funnel while cooling the reaction flask in an ice bath The product was extracted with Et2O (3×50 ml) washed with brine (50 ml) dried (NA2SO4) concentrated Purified by normal phase SiO2 chromatography (7% to 60% EtOAc/hexanes)

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

实验步骤: A 50 ml round-bottom flask equipped with a Dean-Stark distillation setup and condenser was charged with tetrahydro-4H-pyran-4-one (4.61 ml, 50 mmol), methyl cyanoacetate (5.3 ml, 60 mmol), ammonium acetate (1 g, 13 mmol), acetic acid (0.57 ml, 10 mmol) and benzene (30 ml). The mixture was refluxed until no more water collected in the Dean-Stark (2 hours), cooled, benzene (30 ml) added and the organic layer washed with water (50 ml). The aqueous layer was extracted with CH2Cl2 (3×50 ml). The combined organic phase was washed with sat. NaHCO3 (100 ml), brine (100 ml) dried (MgSO4), filtered and concentrated. Purified by normal phase SiO2 chromatography (10 to 60% EtOAc/hexanes) to afford methyl 2-cyano-2-(oxan-4-ylidene)acetate as a colorless oil (6.30 g, 70%, m/z: 181.1 [M+H]+ observed). A 50 ml round-bottom flask equipped with a Dean-Stark distillation setup and condenser collected in the Dean-Stark (2 hours) cooled benzene (30 ml) added the organic layer washed with water (50 ml) The aqueous layer was extracted with CH2Cl2 (3×50 ml) The combined organic phase was washed with sat. NaHCO3 (100 ml), brine (100 ml) dried (MgSO4) filtered concentrated Purified by normal phase SiO2 chromatography (10 to 60% EtOAc/hexanes)