2,3-环氧丙基膦酸二乙基酯

反应条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-fluoro-3-methylphenylmagnesium bromide (0.5M in Et2O, 15.5 mL, 7.75 mmol) in THF (10 mL) at −30° C. was added Cul (196 mg, 1.03 mmol) and the reaction mixture was stirred for 10 minutes. The reaction mixture was warmed to −15° C. and oxiranylmethyl-phosphonic acid diethyl ester (1 g, 5.2 mmol) in THF (10 mL) was added. The reaction mixture was stirred at 0° C. for 2 h. Saturated aqueous ammonium chloride was added. and the product was extracted into EtOAc. The organic solution was dried (MgSO4), filtered and concentrated. Purification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes) provided [3-(4-fluoro-3-methyl-phenyl)-2-hydroxy-propyl]-phosphonic acid diethyl ester (1.37 g). The reaction mixture was stirred at 0° C. for 2 h and the product was extracted into EtOAc The organic solution was dried (MgSO4) filtered concentrated Purification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes)

反应条件: temp:-150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-fluoro-3-methylphenylmagnesium bromide (0.5M in Et2O, 15.5 mL, 7.75 mmol) in THF (10 mL) at −30° C. was added Cul (196 mg, 1.03 mmol) and the reaction mixture was stirred for 10 minutes. The reaction mixture was warmed to −150° C. and oxiranylmethyl-phosphonic acid diethyl ester (1 g, 5.2 mmol) in THF (10 mL) was added. The reaction mixture was stirred at 0° C. for 2 h. Saturated aqueous ammonium chloride was added and the product was extracted into EtOAc. The organic solution was dried (MgSO4), filtered and concentrated. Purification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes) provided [3-(4-fluoro-3-methyl-phenyl)-2-hydroxy-propyl]-phosphonic acid diethyl ester (1.37 g). The reaction mixture was stirred at 0° C. for 2 h the product was extracted into EtOAc The organic solution was dried (MgSO4) filtered concentrated Purification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes)

反应条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-fluoro-3-methylphenylmagnesium bromide (0.5M in Et2O, 15.5 mL, 7.75 mmol) in THF (10 mL) at −30° C. was added Cul (196 mg, 1.03 mmol) and the reaction mixture was stirred for 10 minutes. The reaction mixture was warmed to −15° C. and oxiranylmethyl-phosphonic acid diethyl ester (1 g, 5.2 mmol) in THF (10 mL) was added. The reaction mixture was stirred at 0° C. for 2 h. Saturated aqueous ammonium chloride was added. and the product was extracted into EtOAc. The organic solution was dried (MgSO4), filtered and concentrated. Purification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes) provided [3-(4-fluoro-3-methyl-phenyl)-2-hydroxy-propyl]-phosphonic acid diethyl ester (1.37 g). The reaction mixture was stirred at 0° C. for 2 h and the product was extracted into EtOAc The organic solution was dried (MgSO4) filtered concentrated Purification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes)

反应条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-fluoro-3-methylphenylmagnesium bromide (0.5M in Et2O, 15.5 mL, 7.75 mmol) in THF (10 mL) at −30° C. was added Cul (196 mg, 1.03 mmol) and the reaction mixture was stirred for 10 minutes. The reaction mixture was warmed to −15° C. and oxiranylmethyl-phosphonic acid diethyl ester (1 g, 5.2 mmol) in THF (10 mL) was added. The reaction mixture was stirred at 0° C. for 2 h. Saturated aqueous ammonium chloride was added. and the product was extracted into EtOAc. The organic solution was dried (MgSO4), filtered and concentrated. Purification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes) provided [3-(4-fluoro-3-methyl-phenyl)-2-hydroxy-propyl]-phosphonic acid diethyl ester (1.37 g). The reaction mixture was stirred at 0° C. for 2 h and the product was extracted into EtOAc The organic solution was dried (MgSO4) filtered concentrated Purification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes)

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

实验步骤: 47% aqueous hydrobromic acid (82.8 g) was added dropwise to diethyl 2,3-epoxypropylphosphonate (77.6 g) under ice-cooling and with stirring over a five minute interval. After the stirring was continued for an hour under ice-cooling and for 3 hours at ambient temperature, the reaction mixture was extracted with ethyl acetate (500 ml). The ethyl acetate layer was separated, washed three times with saturated aqueous sodium bicarbonate solution (200 ml and 100 ml×2) and twice with saturated aqueous sodium chloride solution (100 ml×2), dried over magnesium sulfate and evaporated to dryness to give oily diethyl 3-bromo-2-hydroxypropylphosphonate (94.7 g). cooling After the stirring was continued for an hour under ice- the reaction mixture was extracted with ethyl acetate (500 ml) The ethyl acetate layer was separated washed three times with saturated aqueous sodium bicarbonate solution (200 ml and 100 ml×2) twice with saturated aqueous sodium chloride solution (100 ml×2), dried over magnesium sulfate evaporated to dryness

反应条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-fluoro-3-methylphenylmagnesium bromide (0.5M in Et2O, 15.5 mL, 7.75 mmol) in THF (10 mL) at −30° C. was added copper (I) iodide, CuI (196 mg, 1.03 mmol) and the reaction mixture was stirred for 10 minutes. The reaction mixture was warmed to −15° C. and oxiranylmethyl-phosphonic acid diethyl ester (1 g, 5.2 mmol) in THF (10 mL) was added. The reaction mixture was stirred at 0° C. for 2 h. Saturated aqueous ammonium chloride was added and the product was extracted into EtOAc. The organic solution was dried (MgSO4), filtered and concentrated. Purification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes) provided [3-(4-fluoro-3-methyl-phenyl)-2-hydroxy-propyl]-phosphonic acid diethyl ester (1.37 g). The reaction mixture was stirred at 0° C. for 2 h the product was extracted into EtOAc The organic solution was dried (MgSO4) filtered concentrated Purification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes)

反应条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-fluoro-3-methylphenylmagnesium bromide (0.5M in Et2O, 15.5 mL, 7.75 mmol) in THF (10 mL) at −30° C. was added copper (I) iodide, CuI (196 mg, 1.03 mmol) and the reaction mixture was stirred for 10 minutes. The reaction mixture was warmed to −15° C. and oxiranylmethyl-phosphonic acid diethyl ester (1 g, 5.2 mmol) in THF (10 mL) was added. The reaction mixture was stirred at 0° C. for 2 h. Saturated aqueous ammonium chloride was added and the product was extracted into EtOAc. The organic solution was dried (MgSO4), filtered and concentrated. Purification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes) provided [3-(4-fluoro-3-methyl-phenyl)-2-hydroxy-propyl]-phosphonic acid diethyl ester (1.37 g). The reaction mixture was stirred at 0° C. for 2 h the product was extracted into EtOAc The organic solution was dried (MgSO4) filtered concentrated Purification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes)

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

实验步骤: (1)-(a) 47% Aqueous hydrobromic acid (82.8 g) was added dropwise to diethyl 2,3-epoxypropylphosphonate (77.6 g) under ice-cooling and with stirring over a five minutes interval. After the stirring was continued for an hour under ice-cooling and for 3 hours at ambient temperature, the reaction mixture was extracted with ethyl acetate (500 ml). The ethyl acetate layer was separated, washed three times with saturated aqueous sodium bicarbonate solution (200 ml and 100 ml×2) and twice with saturated aqueous sodium chloride solution (100 ml×2), dried over magnesium sulfate and evaporated to dryness to give oily diethyl 3-bromo-2-hydroxypropylphosphonate (94.7 g) cooling After the stirring was continued for an hour under ice- the reaction mixture was extracted with ethyl acetate (500 ml) The ethyl acetate layer was separated washed three times with saturated aqueous sodium bicarbonate solution (200 ml and 100 ml×2) twice with saturated aqueous sodium chloride solution (100 ml×2), dried over magnesium sulfate evaporated to dryness

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

实验步骤: A mixture of diethyl 2,3-epoxypropylphosphonate (14.55 g), 1,2,4-triazole (5.18 g), potassium carbonate (10.35 g) and methyl ethyl ketone (220 ml) was heated under reflux for four hours. The supernatant liquid was decanted from a sticky residue and evaporated under reduced pressure. The crude product was purified by preparative high performance liquid chromatography (using a Waters LC 500 apparatus, silica as solid phase, and ethanol: ether in the proportion of 1:2 by volume as the liquid phase) to give diethyl 2-hydroxy-3(1,2,4-triazol-1-yl)propylphosphonate (7.5 g) as a pale yellow viscous oil. The identity of the product was confirmed by examination of its infra-red; mass; and proton, P31 and C13 nuclear magnetic resonance spectra, which were all consistent with the structure assigned. was heated under reflux for four hours The supernatant liquid was decanted from a sticky residue evaporated under reduced pressure The crude product was purified by preparative high performance liquid chromatography (

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

实验步骤: (1)-(a) 47% Aqueous hydrobromic acid (82.8 g) was added dropwise to diethyl 2,3-epoxypropylphosphonate (77.6 g) under ice-cooling and with stirring over a five minutes interval. After the stirring was continued for an hour under ice-cooling and for 3 hours at ambient temperature, the reaction mixture was extracted with ethyl acetate (500 ml). The ethyl acetate layer was separated, washed three times with saturated aqueous sodium bicarbonate solution (200 ml and 100 ml×2) and twice with saturated aqueous sodium chloride solution (100 ml×2), dried over magnesium sulfate and evaporated to dryness to give oily diethyl 3-bromo-2-hydroxypropylphosphonate (94.7 g) cooling After the stirring was continued for an hour under ice- the reaction mixture was extracted with ethyl acetate (500 ml) The ethyl acetate layer was separated washed three times with saturated aqueous sodium bicarbonate solution (200 ml and 100 ml×2) twice with saturated aqueous sodium chloride solution (100 ml×2), dried over magnesium sulfate evaporated to dryness

反应条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-fluoro-3-methylphenylmagnesium bromide (0.5M in Et2O, 15.5 mL, 7.75 mmol) in THF (10 mL) at −30° C. was added Cul (196 mg, 1.03 mmol) and the reaction mixture was stirred for 10 minutes. The reaction mixture was warmed to −15° C. and oxiranylmethyl-phosphonic acid diethyl ester (1 g, 5.2 mmol) in THF (10 mL) was added. The reaction mixture was stirred at 0° C. for 2 h. Saturated aqueous ammonium chloride was added and the product was extracted into EtOAc. The organic solution was dried (MgSO4), filtered and concentrated. Purification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes) provided [3-(4-fluoro-3-methyl-phenyl)-2-hydroxy-propyl]-phosphonic acid diethyl ester (1.37 g). The reaction mixture was stirred at 0° C. for 2 h the product was extracted into EtOAc The organic solution was dried (MgSO4) filtered concentrated Purification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes)

反应条件: temp:-150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-fluoro-3-methylphenylmagnesium bromide (0.5M in Et2O, 15.5 mL, 7.75 mmol) in THF (10 mL) at −30° C. was added Cul (196 mg, 1.03 mmol) and the reaction mixture was stirred for 10 minutes. The reaction mixture was warmed to −150° C. and oxiranylmethyl-phosphonic acid diethyl ester (1 g, 5.2 mmol) in THF (10 mL) was added. The reaction mixture was stirred at 0° C. for 2 h. Saturated aqueous ammonium chloride was added and the product was extracted into EtOAc. The organic solution was dried (MgSO4), filtered and concentrated. Purification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes) provided [3-(4-fluoro-3-methyl-phenyl)-2-hydroxy-propyl]-phosphonic acid diethyl ester (1.37 g). The reaction mixture was stirred at 0° C. for 2 h the product was extracted into EtOAc The organic solution was dried (MgSO4) filtered concentrated Purification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes)