2-dimethoxyphosphorylethanol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (2-hydroxy-ethyl)-phosphonic acid dimethyl ester (0.250 g, 1.62 mmol) in dichloromethane (4 mL) was added 2,6-lutidine (0.284 mL, 2.44 mmol). The reaction mixture was cooled to −40° C. and trifluoromethanesulfonic anhydride (0.355 mL, 2.11 mmol) was added. The mixture stirred in the cold bath under an inert atmosphere for 2 hours at which point the reaction was completed as shown by 31P NMR (CDCl3) δ 25.7. The mixture was partitioned between dichloromethane and water both cooled by an ice-water bath. The organic phase was washed with brine, dried (MgSO4), and concentrated in vacuo to afford trifluoromethanesulfonic acid dimethoxy-phosphoryl-2-ethyl ester 185 as an oil which was immediately carried forward with no further purification or characterization. The mixture was partitioned between dichloromethane and water both cooled by an ice-water bath The organic phase was washed with brine dried (MgSO4) concentrated in vacuo

反応条件: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (2-hydroxy-ethyl)-phosphonic acid dimethyl ester (0.250 g, 1.62 mmol) in dichloromethane (4 mL) was added 2,6-lutidine (0.284 mL, 2.44 mmol). The reaction mixture was cooled to −40° C. and trifluoromethanesulfonic anhydride (0.355 mL, 2.11 mmol) was added. The mixture stirred in the cold bath under an inert atmosphere for 2 hours at which point the reaction was completed as shown by 31P NMR (CDCl3) δ 25.7. The mixture was partitioned between dichloromethane and water both cooled by an ice-water bath. The organic phase was washed with brine, dried (MgSO4), and concentrated in vacuo to afford trifluoromethanesulfonic acid dimethoxy-phosphoryl-2-ethyl ester 185 as an oil which was immediately carried forward with no further purification or characterization. The mixture was partitioned between dichloromethane and water both cooled by an ice-water bath The organic phase was washed with brine dried (MgSO4) concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9 was prepared from BM-957 and dimethyl (2-hydroxyethyl)phosphonate according general procedure V. MS (ESI): m/z 1173.42 (M+H)+.

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 86.3 g (850 mmol) 2-(chloromethyl)-acrylonitrile are added dropwise at room temperature to a solution of 130.9 g (850 mmol) 2-hydroxyethylphosphonic acid dimethylester, 85.9 g (850 mmol) triethylamine (TEA) and 40 mg phenothiazine (stabilizer) in 1 l THF. Subsequently, the mixture is heated for 6 hours at 65° C. under reflux. 9.1 g (90 mmol) TEA and 9.1 g (90 mmol) 2-(chloromethyl)-acrylonitrile are once again added one after the other and the mixture is heated for a further 24 hours under reflux. After the reaction mixture has cooled, the formed deposit of TEA hydrochloride is filtered out and is washed twice with 50 ml THF. After the THF phases have been concentrated on the rotary evaporator, the residual raw product is taken up in 650 ml methylene chloride and washed twice with water. After it has been dried over anhydrous sodium sulphate, the mixture is concentrated and the residual liquid undergoes fractional distillation in the fine vacuum. 101.0 g (54% yield) of a colourless liquid results at b.p. 150° C. (0.05 mbar). under reflux is heated for a further 24 hours under reflux After the reaction mixture has cooled the formed deposit of TEA hydrochloride is filtered out and is washed twice with 50 ml THF After the THF phases have been concentrated on the rotary evaporator washed twice with water After it has been dried over anhydrous sodium sulphate the mixture is concentrated distillation in the fine vacuum

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 86.3 g (850 mmol) 2-(chloromethyl)-acrylonitrile are added dropwise at room temperature to a solution of 130.9 g (850 mmol) 2-hydroxyethylphosphonic acid dimethylester, 85.9 g (850 mmol) triethylamine (TEA) and 40 mg phenothiazine (stabilizer) in 1 l THF. Subsequently, the mixture is heated for 6 hours at 65° C. under reflux. 9.1 g (90 mmol) TEA and 9.1 g (90 mmol) 2-(chloromethyl)-acrylonitrile are once again added one after the other and the mixture is heated for a further 24 hours under reflux. After the reaction mixture has cooled, the formed deposit of TEA hydrochloride is filtered out and is washed twice with 50 ml THF. After the THF phases have been concentrated on the rotary evaporator, the residual raw product is taken up in 650 ml methylene chloride and washed twice with water. After it has been dried over anhydrous sodium sulphate, the mixture is concentrated and the residual liquid undergoes fractional distillation in the fine vacuum. 101.0 g (54% yield) of a colourless liquid results at b.p. 150° C. (0.05 mbar). under reflux is heated for a further 24 hours under reflux After the reaction mixture has cooled the formed deposit of TEA hydrochloride is filtered out and is washed twice with 50 ml THF After the THF phases have been concentrated on the rotary evaporator washed twice with water After it has been dried over anhydrous sodium sulphate the mixture is concentrated distillation in the fine vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 50 g of 2-acetoxyethane phosphonic acid dimethyl ester in 100 ml of anhydrous methanol is heated to 65°-70°C for 5 hours, while adding one drop of concentrated sulfuric acid. A mixture of methyl acetate/methanol is removed continuously by distillation in the course of the reaction. After a distillation under reduced pressure 33.5 g of 2-hydroxyethane-phosphonic acid dimethyl ester are obtained, corresponding to a yield of 85% of the theoretical. is removed continuously by distillation in the course of the reaction After a distillation under reduced pressure 33.5 g of 2-hydroxyethane-phosphonic acid dimethyl ester are obtained, corresponding to a yield of 85% of the theoretical

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 100 g of 2-acetoxyethane-phosphonic acid dimethyl ester in 100 ml of anhydrous methanol -- 4 g of p-toluenesulfonic acid being added -- is heated for 5 hours to 65°-75°C while removing simultaneously by distillation a mixture of methyl acetate/methanol. After distillation under reduced pressure, 59 g of 2-hydroxyethane-phosphonic acid dimethyl ester are obtained, corresponding to a yield of 75% of the theoretical. is heated for 5 hours to 65°-75°C while removing simultaneously by distillation a mixture of methyl acetate/methanol After distillation under reduced pressure, 59 g of 2-hydroxyethane-phosphonic acid dimethyl ester are obtained, corresponding to a yield of 75% of the theoretical

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 50 g of 2-acetoxyethane-phosphonic acid dimethyl ester in 100 ml of anhydrous methanol is mixed with 0.5 g of KOH and heated to 65°-70°C for 5 hours while simultaneously removing a mixture of methyl acetate/methanol by distillation. The crude product is submitted to distillation under reduced pressure, 34 g of 2-hydroxyethane-phosphonic acid dimethyl ester are obtained, corresponding to a yield of 86.5% of the theoretical. heated to 65°-70°C for 5 hours while simultaneously removing a mixture of methyl acetate/methanol by distillation The crude product is submitted to distillation under reduced pressure, 34 g of 2-hydroxyethane-phosphonic acid dimethyl ester are obtained, corresponding to a yield of 86.5% of the theoretical

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 600 g of 2-acetoxyethane-phosphonic acid dimethyl ester are heated for 5 hours to 65°-75°C in 600 ml of methanol to which 3 g of sodium had been added. A mixture of methyl acetate/methanol is removed continuously by distillation. The reaction being terminated, the residue is submitted to distillation under reduced pressure, 369 g of 2-hydroxyethane-phosphonic acid dimethyl ester (boiling point: 122°C/0.2 torr) are obtained, corresponding to a yield of 84% in the theoretical. had been added is removed continuously by distillation The reaction being terminated the residue is submitted to distillation under reduced pressure, 369 g of 2-hydroxyethane-phosphonic acid dimethyl ester (boiling point: 122°C/0.2 torr) are obtained, corresponding to a yield of 84% in the theoretical

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dimethyl 2-vinylsulfonyloxyethylphosphonate was prepared in the same way as in Example 1 from 3.8 g of dimethyl 2-hydroxyethylphosphonate, 1.9 g of pyridine and 4.0 g of 2-chloroethylsulfonyl chloride. The yield was 20 mol%. The NMR spectrum (CDCl3) of this product was as follows:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3.9 g. of dimethyl 2-hydroxyethylphosphonate and 5.9 g of pyridine were dissolved in 40 ml. of dry diethyl ether, and the solution was cooled with ice to -5° C. A solution of 6.0 g of γ-bromopropylsulfonyl chloride in 30 ml. of dry diethyl ether was added dropwise to the cooled solution by means of a dropping funnel. After the addition, the mixed solution was allowed to stand for 24 hours at 0° to 5° C. The reaction mixture was poured into 50 ml. of 5% hydrochloric acid, and extracted with diethyl ether. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off at reduced pressure. The product was further dried at room temperature at 0.7 mmHg for 18 hours to afford dimethyl 2-(3-bromopropyl-sulfonyloxy)ethylphosphonate as a colorless oil in a yield of 75 mol %. The product showed the following characteristic values. After the addition The reaction mixture was poured into 50 ml of 5% hydrochloric acid, and extracted with diethyl ether The extract was dried over anhydrous sodium sulfate the solvent was distilled off at reduced pressure The product was further dried at room temperature at 0.7 mmHg for 18 hours