ethyl diethoxyphosphorylmethanesulfonate

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

実験手順: Mineral oil was removed from sodium hydride (84.4 mg, 2.110 mmol) with heptane (2×4 ml) under a nitrogen atmosphere after which anhydrous tetrahydrofuran (10 ml) was added. To this suspension was added dropwise a solution of ethyl (diethoxyphosphoryl)methanesulfonate (500 mg, 1.921 mmol) in anhydrous tetrahydrofuran (10 ml) upon which hydrogen gas evolved from the mixture. After 5 minutes a clear slightly yellow solution was obtained. Isobutyraldehyde (200 μl, 2.191 mmol) was added and the resulting mixture was stirred at room temperature over night. The reaction mixture was quenched with a mixture of brine (50 ml) and aqueous saturated ammonium chloride solution (150 ml). The aqeuous mixture was extracted with dichloromethane (3×70 ml), the combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to yield 550 mg of a slightly yellow oil that was used directly in the next step. was added After 5 minutes a clear slightly yellow solution was obtained The reaction mixture was quenched with a mixture of brine (50 ml) and aqueous saturated ammonium chloride solution (150 ml) The aqeuous mixture was extracted with dichloromethane (3×70 ml) the combined organic layers were dried over sodium sulfate concentrated under reduced pressure to yield 550 mg of a slightly yellow oil that

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

実験手順: A solution of ethyl methanesulfonate (4.14 mL, 40.2 mmol) in anhydrous tetrahydrofuran (100 ml) was cooled to −78° C. under a nitrogen atmosphere. N-Butyllithium (20 ml, 50.0 mmol) was added slowly in 7 minutes after which stirring was continued for 15 minutes. Diethyl phosphorochloridate (4.36 mL, 30.2 mmol) was added, the reaction mixture was stirred for 2.5 h, the cooling bath was removed and the mixture was allowed to reach room temperature. The reaction mixture was quenched with aqueous saturated ammonium chloride (150 ml) and the resulting mixture was extracted with EtOAc (2×100 ml). The combined extracts were dried over sodium sulfate and concentrated under reduced pressure to yield 9.20 g of a yellow oil. The oil was purified over silicagel (600 g) using a gradient of ethyl acetate (0-100%) in heptane to yield 1.75 g of the product (6.7 mol, 17%). the reaction mixture was stirred for 2.5 h the cooling bath was removed to reach room temperature The reaction mixture was quenched with aqueous saturated ammonium chloride (150 ml) the resulting mixture was extracted with EtOAc (2×100 ml) The combined extracts were dried over sodium sulfate concentrated under reduced pressure

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

実験手順: A solution of ethyl methanesulfonate (4.27 mL, 40.3 mmol) in 100 mL of dry THF was treated at -78° C. with 19.3 mL (44.4 mmol) of n-BuLi in hexane. After 15 min. diethyl chlorophosphate (3.30 ml, 22.2 mmol) was added. The solution was kept at -78° C. for 0.5 h and allowed to stay at -50° C. for 1 h. Saturated ammonium chloride (75 mL) was added to the solution and the mixture warmed to room temperature. The mixture was concentrated (THF removed), diluted with water and extracted with methylene chloride (3×70 mL). The combined organic fractions were dried (MgSO4), concentrated and purified by distillation to yield 3.86 g (70%) of title compound. to stay at -50° C. for 1 h The mixture was concentrated (THF removed) diluted with water extracted with methylene chloride (3×70 mL) The combined organic fractions were dried (MgSO4) concentrated purified by distillation

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

実験手順: A solution of ethyl methanesulfonate (4.27 mL, 40.3 mmol) in 100 mL of dry THF was treated at -78° C. with 19.3 mL (44.4 mmol) of n-BuLi in hexane. After 15 min. diethyl chlorophosphate (3.30 ml, 22.2 mmol) was added. The solution was kept at -78° C. for 0.5 h and allowed to stay at -50° C. for 1 h. Saturated ammonium chloride (75 mL) was added to the solution and the mixture warmed to room temperature. The mixture was concentrated (THF removed), diluted with water and extracted with methylene chloride (3×70 mL). The combined organic fractions were dried (MgSO4), concentrated and purified by distillation to yield 3.86 g (70%) of title compound. to stay at -50° C. for 1 h The mixture was concentrated (THF removed) diluted with water extracted with methylene chloride (3×70 mL) The combined organic fractions were dried (MgSO4) concentrated purified by distillation

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

実験手順: A solution of ethyl methanesulfonate (4.27 mL, 40.3 mmol) in 100 mL of dry THF was treated at -78° C. with 19.3 mL (44.4 mmol) of n-BuLi in hexane. After 15 min. diethyl chlorophosphate (3.30 ml, 22.2 mmol) was added. The solution was kept at -78° C. for 0.5 h and allowed to stay at -50° C. for 1 h. Saturated ammonium chloride (75 mL) was added to the solution and the mixture warmed to room temperature. The mixture was concentrated (THF removed), diluted with water and extracted with methylene chloride (3×70 mL). The combined organic fractions were dried (MgSO4), concentrated and purified by distillation to yield 3.86 g (70%) of title compound. to stay at -50° C. for 1 h The mixture was concentrated (THF removed) diluted with water extracted with methylene chloride (3×70 mL) The combined organic fractions were dried (MgSO4) concentrated purified by distillation

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (diethoxy-phosphoryl)-methanesulfonic acid ethyl ester (7.991 g, 0.03070 mol) in THF (100 mL), at −78° C. under an atmosphere of nitrogen, was added dropwise 2.5M n-butyllithium in hexane (13 mL), and the solution was stirred for 30 minutes. Freshly prepared 6-(6-chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]-dioxole-4-carbaldehyde (13.10 g, 0.03026 mol) in THF (100 mL) was added over 15 min at −78° C. The reaction was allowed to slowly warm to −10° C. over 4 hours with stirring. The reaction was quenched with water (400 mL) and 5M ammonium chloride in water (100 mL) and extracted with methylene chloride (600 mL). The organic phase was concentrated in vacuo and the residue was purified by flash chromatography (30 to 100% EtOAc:hexanes) to yield the product as a foam (10.5 g, 81%). with stirring The reaction was quenched with water (400 mL) and 5M ammonium chloride in water (100 mL) extracted with methylene chloride (600 mL) The organic phase was concentrated in vacuo the residue was purified by flash chromatography (30 to 100% EtOAc:hexanes)

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (diethoxy-phosphoryl)-methanesulfonic acid ethyl ester (7.991 g, 0.03070 mol) in THF (100 mL), at −78° C. under an atmosphere of nitrogen, was added dropwise 2.5M n-butyllithium in hexane (13 mL), and the solution was stirred for 30 minutes. Freshly prepared 6-(6-chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]-dioxole-4-carbaldehyde (13.10 g, 0.03026 mol) in THF (100 mL) was added over 15 min at −78° C. The reaction was allowed to slowly warm to −10° C. over 4 hours with stirring. The reaction was quenched with water (400 mL) and 5M ammonium chloride in water (100 mL) and extracted with methylene chloride (600 mL). The organic phase was concentrated in vacuo and the residue was purified by flash chromatography (30 to 100% EtOAc:hexanes) to yield the product as a foam (10.5 g, 81%). with stirring The reaction was quenched with water (400 mL) and 5M ammonium chloride in water (100 mL) extracted with methylene chloride (600 mL) The organic phase was concentrated in vacuo the residue was purified by flash chromatography (30 to 100% EtOAc:hexanes)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methanesulfonic acid, ethyl ester (11.00 mL, 0.1068 mol) in THF (200.0 mL, 2.466 mol) at −78° C. was added 2.500 M of n-butyllithium in hexane (50.00 mL) over 15 minutes and the mixture was stirred for 20 minutes. Phosphorochloridic acid, diethyl ester (10.0 mL, 0.0694 mol) was added to the mixture at −78° C. The mixture was stirred for 3.5 hours, allowing to warm to 0° C. The reaction was quenched with 5M ammonium chloride in water (100 mL) and the mixture was concentrated in vacuo to remove THF. The aqueous was extracted with EtOAc (2×150 mL) and the organics were combined and concentrated in vacuo. The product was purified by flash chromatography (0 to 100% EtOAc/Hexanes) to yield the product as an oil (9.07 g, 50%+10.4 g of a mixed fraction). The mixture was stirred for 3.5 hours The reaction was quenched with 5M ammonium chloride in water (100 mL) the mixture was concentrated in vacuo to remove THF The aqueous was extracted with EtOAc (2×150 mL) concentrated in vacuo The product was purified by flash chromatography (0 to 100% EtOAc/Hexanes)

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

実験手順: Mineral oil was removed from sodium hydride (84.4 mg, 2.110 mmol) with heptane (2×4 ml) under a nitrogen atmosphere after which anhydrous tetrahydrofuran (10 ml) was added. To this suspension was added dropwise a solution of ethyl (diethoxyphosphoryl)methanesulfonate (500 mg, 1.921 mmol) in anhydrous tetrahydrofuran (10 ml) upon which hydrogen gas evolved from the mixture. After 5 minutes a clear slightly yellow solution was obtained. Isobutyraldehyde (200 μl, 2.191 mmol) was added and the resulting mixture was stirred at room temperature over night. The reaction mixture was quenched with a mixture of brine (50 ml) and aqueous saturated ammonium chloride solution (150 ml). The aqeuous mixture was extracted with dichloromethane (3×70 ml), the combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to yield 550 mg of a slightly yellow oil that was used directly in the next step. was added After 5 minutes a clear slightly yellow solution was obtained The reaction mixture was quenched with a mixture of brine (50 ml) and aqueous saturated ammonium chloride solution (150 ml) The aqeuous mixture was extracted with dichloromethane (3×70 ml) the combined organic layers were dried over sodium sulfate concentrated under reduced pressure to yield 550 mg of a slightly yellow oil that

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

実験手順: A solution of ethyl methanesulfonate (4.14 mL, 40.2 mmol) in anhydrous tetrahydrofuran (100 ml) was cooled to −78° C. under a nitrogen atmosphere. N-Butyllithium (20 ml, 50.0 mmol) was added slowly in 7 minutes after which stirring was continued for 15 minutes. Diethyl phosphorochloridate (4.36 mL, 30.2 mmol) was added, the reaction mixture was stirred for 2.5 h, the cooling bath was removed and the mixture was allowed to reach room temperature. The reaction mixture was quenched with aqueous saturated ammonium chloride (150 ml) and the resulting mixture was extracted with EtOAc (2×100 ml). The combined extracts were dried over sodium sulfate and concentrated under reduced pressure to yield 9.20 g of a yellow oil. The oil was purified over silicagel (600 g) using a gradient of ethyl acetate (0-100%) in heptane to yield 1.75 g of the product (6.7 mol, 17%). the reaction mixture was stirred for 2.5 h the cooling bath was removed to reach room temperature The reaction mixture was quenched with aqueous saturated ammonium chloride (150 ml) the resulting mixture was extracted with EtOAc (2×100 ml) The combined extracts were dried over sodium sulfate concentrated under reduced pressure

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

実験手順: A solution of ethyl methanesulfonate (4.14 mL, 40.2 mmol) in anhydrous tetrahydrofuran (100 ml) was cooled to −78° C. under a nitrogen atmosphere. N-Butyllithium (20 ml, 50.0 mmol) was added slowly in 7 minutes after which stirring was continued for 15 minutes. Diethyl phosphorochloridate (4.36 mL, 30.2 mmol) was added, the reaction mixture was stirred for 2.5 h, the cooling bath was removed and the mixture was allowed to reach room temperature. The reaction mixture was quenched with aqueous saturated ammonium chloride (150 ml) and the resulting mixture was extracted with EtOAc (2×100 ml). The combined extracts were dried over sodium sulfate and concentrated under reduced pressure to yield 9.20 g of a yellow oil. The oil was purified over silicagel (600 g) using a gradient of ethyl acetate (0-100%) in heptane to yield 1.75 g of the product (6.7 mol, 17%). the reaction mixture was stirred for 2.5 h the cooling bath was removed to reach room temperature The reaction mixture was quenched with aqueous saturated ammonium chloride (150 ml) the resulting mixture was extracted with EtOAc (2×100 ml) The combined extracts were dried over sodium sulfate concentrated under reduced pressure

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

実験手順: A solution of ethyl methanesulfonate (4.27 mL, 40.3 mmol) in 100 mL of dry THF was treated at -78° C. with 19.3 mL (44.4 mmol) of n-BuLi in hexane. After 15 min. diethyl chlorophosphate (3.30 ml, 22.2 mmol) was added. The solution was kept at -78° C. for 0.5 h and allowed to stay at -50° C. for 1 h. Saturated ammonium chloride (75 mL) was added to the solution and the mixture warmed to room temperature. The mixture was concentrated (THF removed), diluted with water and extracted with methylene chloride (3×70 mL). The combined organic fractions were dried (MgSO4), concentrated and purified by distillation to yield 3.86 g (70%) of title compound. to stay at -50° C. for 1 h The mixture was concentrated (THF removed) diluted with water extracted with methylene chloride (3×70 mL) The combined organic fractions were dried (MgSO4) concentrated purified by distillation