3-diethoxyphosphorylpropan-1-ol

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A solution of (2-ethoxy-ethyl)-phosphonic acid diethyl ester (0.500 g, 2.1 mmol) in ether (8.5 mL) and THF (1.5 mL) was treated with lithium borohydride. The reaction mixture stirred at room temperature for 1 hour and was then concentrated in vacuo. The crude mixture was partitioned between dichloromethane and water. The organic phase was washed with saturated NaHCO3 and brine, dried (MgSO4), then concentrated in vacuo. The residue was purified by silica gel chromatography (5/95—methanol/dichloromethane) to afford (3-hydroxy-propyl)-phosphonic acid diethyl ester 178 (0.100 g, 24%) as an oil: 1H NMR (CDCl3) δ 4.1 (m, 4H), 3.7 (m, 2H), 2.95 (bs, 1H), 1.85 (m, 4H), 1.30 (t, 3H); 31P NMR (CDCl3) δ 33.26; MS: 197 (M+1). was then concentrated in vacuo The crude mixture was partitioned between dichloromethane and water The organic phase was washed with saturated NaHCO3 and brine dried (MgSO4) concentrated in vacuo The residue was purified by silica gel chromatography (5/95—methanol/dichloromethane)

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

実験手順: Diethyl-3-hydroxypropylphosphonate (steps 1 and 2) is prepared from diethyl-3-bromopropylphosphonate. Diethyl-3-bromopropylphosphonate (12.0 g, 46 mmol), prepared by the method of Eberhard, A., et al, J Am Chem Soc (1965) 87:253-260) was stirred with 12.0 g NaOAc.3H2O in 125 ml DMF heated in a steam bath. The reaction was evaporated to dryness in vacuo after 2 hours and partitioned between H2O and EtOAc. extracting the aqueous layer five times. The ethyl acetate extract was washed once with brine, dried with Na2SO4, filtered, and evaporated to dryness in vacuo to yield 9.8 g light yellow oil (89%). 1H NMR (CDCl3) δ1.3 (tr, 6 H), 1.5-2.0 (m, 4 H), 2.03 (s, 3 H), 4.1 (dq, 6 H): thin-layer chromatography on SiGF developed with 2:1 EtOAc:CH2Cl2 gave Rf 0.30. The isolated diethyl-3-acetoxypropylphosphonate (9.8 g, 41 mmol) in 200 ml abs. EtOH was stirred with 30 ml Dowex 50 (H+) which had been rinsed three times each with H2O and EtOH. After 41/2 days at room temperature, another 10 ml of similarly prepared resin was added. Six hours later, the reaction was filtered and evaporated in vacuo. The quantitative yield of yellow oil was purified by dry column chromatography on 400 g silica packed in a 2.75-inch flat diameter nylon tube. The column was eluted with 1:9 MeOH:EtOAc and the appropriate fractions were cut and slurried with 1:1 MeOH:EtOAc. Filtration and evaporation in vacuo afforded 5.33 g (66%) pale yellow oil, which is the diethyl ester of 3-hydroxypropyl phosphonic acid. 1H NMR (CDCl3, D2O): δ1.3 (tr, 6 H), 1.6-2.08 (m, 4 H), 3.67 (tr. 2 H), 4.13 (dq. 4 H); thin-layer chromatography on SiGF developed with 1:9 MeOH:EtOAc gave an Rf of 0.57. heated in a steam bath The reaction was evaporated to dryness in vacuo after 2 hours partitioned between H2O and EtOAc extracting the aqueous layer five times The ethyl acetate extract was washed once with brine dried with Na2SO4 filtered evaporated to dryness in vacuo

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A solution of (2-ethoxy-ethyl)-phosphonic acid diethyl ester (0.500 g, 2.1 mmol) in ether (8.5 mL) and THF (1.5 mL) was treated with lithium borohydride. The reaction mixture stirred at room temperature for 1 hour and was then concentrated in vacuo. The crude mixture was partitioned between dichloromethane and water. The organic phase was washed with saturated NaHCO3 and brine, dried (MgSO4), then concentrated in vacuo. The residue was purified by silica gel chromatography (5/95—methanol/dichloromethane) to afford (3-hydroxy-propyl)-phosphonic acid diethyl ester 178 (0.100 g, 24%) as an oil: 1H NMR (CDCl3) δ 4.1 (m, 4H), 3.7 (m, 2H), 2.95 (bs, 1H), 1.85 (m, 4H), 1.30 (t, 3H); 31P NMR (CDCl3) δ 33.26; MS: 197 (M+1). was then concentrated in vacuo The crude mixture was partitioned between dichloromethane and water The organic phase was washed with saturated NaHCO3 and brine dried (MgSO4) concentrated in vacuo The residue was purified by silica gel chromatography (5/95—methanol/dichloromethane)

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

実験手順: Diethyl-3-hydroxypropylphosphonate (steps 1 and 2) is prepared from diethyl-3-bromopropylphosphonate. Diethyl-3-bromopropylphosphonate (12.0 g, 46 mmol), prepared by the method of Eberhard, A., et al, J Am Chem Soc (1965) 87:253-260) was stirred with 12.0 g NaOAc.3H2O in 125 ml DMF heated in a steam bath. The reaction was evaporated to dryness in vacuo after 2 hours and partitioned between H2O and EtOAc. extracting the aqueous layer five times. The ethyl acetate extract was washed once with brine, dried with Na2SO4, filtered, and evaporated to dryness in vacuo to yield 9.8 g light yellow oil (89%). 1H NMR (CDCl3) δ1.3 (tr, 6 H), 1.5-2.0 (m, 4 H), 2.03 (s, 3 H), 4.1 (dq, 6 H): thin-layer chromatography on SiGF developed with 2:1 EtOAc:CH2Cl2 gave Rf 0.30. The isolated diethyl-3-acetoxypropylphosphonate (9.8 g, 41 mmol) in 200 ml abs. EtOH was stirred with 30 ml Dowex 50 (H+) which had been rinsed three times each with H2O and EtOH. After 41/2 days at room temperature, another 10 ml of similarly prepared resin was added. Six hours later, the reaction was filtered and evaporated in vacuo. The quantitative yield of yellow oil was purified by dry column chromatography on 400 g silica packed in a 2.75-inch flat diameter nylon tube. The column was eluted with 1:9 MeOH:EtOAc and the appropriate fractions were cut and slurried with 1:1 MeOH:EtOAc. Filtration and evaporation in vacuo afforded 5.33 g (66%) pale yellow oil, which is the diethyl ester of 3-hydroxypropyl phosphonic acid. 1H NMR (CDCl3, D2O): δ1.3 (tr, 6 H), 1.6-2.08 (m, 4 H), 3.67 (tr. 2 H), 4.13 (dq. 4 H); thin-layer chromatography on SiGF developed with 1:9 MeOH:EtOAc gave an Rf of 0.57. heated in a steam bath The reaction was evaporated to dryness in vacuo after 2 hours partitioned between H2O and EtOAc extracting the aqueous layer five times The ethyl acetate extract was washed once with brine dried with Na2SO4 filtered evaporated to dryness in vacuo