2-chloro-1,3,2lambda5-dioxaphospholane 2-oxide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution containing 1.275 g of dl-trans-2-hexadecyloxymethyl-3-hydroxytetrahydrofuran (prepared as described in Preparation 14), 1.060 g of 2-chloro-2-oxo-1,3,2-dioxaphospholane and 1.30 ml of diisopropylethylamine in 20 ml of 1,2-dichloroethane was heated, with stirring, at 80° C. for 16 hours. The mixture was then cooled, and the solvent was removed by distillation under reduced pressure. The residue was then dissolved in 15 ml of acetonitrile. 3.0 g of trimethylamine gas were passed through and dissolved in the solution, and the resulting reaction mixture was heated in a sealed tube at 80° C. for 18 hours. It was then cooled, and the reaction mixture was evaporated to dryness. The residue was subjected to column chromatography using 50 g of silica gel. The crude substance obtained from the fraction eluted with a 60:35:5 by volume mixture of methylene chloride, methanol and water was further purified by chromatography through two silica gel Lobar B columns. The fraction eluted with the same solvent system as described above gave 1.257 g of the title compound as a white powder, melting at 213°-223° C. was heated The mixture was then cooled the solvent was removed by distillation under reduced pressure The residue was then dissolved in 15 ml of acetonitrile dissolved in the solution the resulting reaction mixture was heated in a sealed tube at 80° C. for 18 hours It was then cooled the reaction mixture was evaporated to dryness The crude substance obtained from the fraction eluted with a 60:35:5 by volume mixture of methylene chloride, methanol and water was further purified by chromatography through two silica gel Lobar B columns The fraction eluted with the same solvent system

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Hydroxyethyl acrylate (11.5 ml, 0.1M) and triethylamine (14.6 ml) in dry diethyl ether (250 ml) were cooled to -25° C. under nitrogen as a solution of 2-chloro-2-oxo-1,3,2-dioxaphospholane (14.3 g) in dry diethyl ether was added over 20 minutes. The mixture was stirred for a further 1 hour at -20° C. and then allowed to warm to 10° C. over a further hour. The precipitate was filtered, washed with ethyl acetate (100 ml) and the combined filtrate and washings evaporated under reduced pressure to give a pale yellow oil (21 g). was added over 20 minutes to warm to 10° C. over a further hour The precipitate was filtered washed with ethyl acetate (100 ml) the combined filtrate and washings evaporated under reduced pressure

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Hydroxyethyl acrylate (11.5 ml, 0.1M) and triethylamine (14.6 ml) in dry diethyl ether (250 ml) were cooled to -25° C. under nitrogen as a solution of 2-chloro-2-oxo-1,3,2-dioxaphospholane (14.3 g) in dry diethyl ether was added over 20 minutes. The mixture was stirred for a further 1 hour at -20° C. and then allowed to warm to 10° C. over a further hour. The precipitate was filtered, washed with ethyl acetate (100 ml) and the combined filtrate and washings evaporated under reduced pressure to give a pale yellow oil (21 g). was added over 20 minutes to warm to 10° C. over a further hour The precipitate was filtered washed with ethyl acetate (100 ml) the combined filtrate and washings evaporated 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 freshly prepared 2-chloro-2-oxo-1,3,2-dioxaphospholane (14.2 g, 0.1M) in dry dichloromethane (30 ml) was added, drop-wise, to a stirred mixture of 2-(tert-butyldimethylsilyloxy)ethanol (17.6 g, 0.1M), triethylamine (18.1 ml), 0.13M) in dry dichloromethane (30 ml) at 0° C. under a nitrogen atmosphere. The mixture was allowed to warm to ambient temperature and was stirred for a further 2 hours. The mixture was filtered and the filtrand washed with n-hexane. The filtrate was evaporated in vacuo, diluted with n-hexane (30 ml) filtered and the filtrate evaporated in vacuo to give a brown oil. The mixture was filtered the filtrand washed with n-hexane The filtrate was evaporated in vacuo diluted with n-hexane (30 ml) filtered the filtrate evaporated in vacuo to give a brown oil

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Hydroxyethyl acrylate (11.5 ml, 0.1M) and triethylamine (14.6 ml) in dry diethyl ether (250 ml) were cooled to -25° C. under nitrogen as a solution of 2-chloro-2-oxo-1,3,2-dioxaphospholane (14.3 g) in dry diethyl ether was added over 20 minutes. The mixture was stirred for a further 1 hour at -20° C. and then allowed to warm to 10° C. over a further hour. The precipitate was filtered, washed with ethyl acetate (100 ml) and the combined filtrate and washings evaporated under reduced pressure to give a pale yellow oil (21 g). was added over 20 minutes to warm to 10° C. over a further hour The precipitate was filtered washed with ethyl acetate (100 ml) the combined filtrate and washings evaporated under reduced pressure

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Hydroxyethyl acrylate (11.5 ml, 0.1M) and triethylamine (14.6 ml) in dry diethyl ether (250 ml) were cooled to -25° C. under nitrogen as a solution of 2-chloro-2-oxo-1,3,2-dioxaphospholane (14.3 g) in dry diethyl ether was added over 20 minutes. The mixture was stirred for a further 1 hour at -20° C. and then allowed to warm to 10° C. over a further hour. The precipitate was filtered, washed with ethyl acetate (100 ml) and the combined filtrate and washings evaporated under reduced pressure to give a pale yellow oil (21 g). was added over 20 minutes to warm to 10° C. over a further hour The precipitate was filtered washed with ethyl acetate (100 ml) the combined filtrate and washings evaporated under reduced pressure

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution containing 1.275 g of dl-trans-2-hexadecyloxymethyl-3-hydroxytetrahydrofuran (prepared as described in Preparation 14), 1.060 g of 2-chloro-2-oxo-1,3,2-dioxaphospholane and 1.30 ml of diisopropylethylamine in 20 ml of 1,2-dichloroethane was heated, with stirring, at 80° C. for 16 hours. The mixture was then cooled, and the solvent was removed by distillation under reduced pressure. The residue was then dissolved in 15 ml of acetonitrile. 3.0 g of trimethylamine gas were passed through and dissolved in the solution, and the resulting reaction mixture was heated in a sealed tube at 80° C. for 18 hours. It was then cooled, and the reaction mixture was evaporated to dryness. The residue was subjected to column chromatography using 50 g of silica gel. The crude substance obtained from the fraction eluted with a 60:35:5 by volume mixture of methylene chloride, methanol and water was further purified by chromatography through two silica gel Lobar B columns. The fraction eluted with the same solvent system as described above gave 1.257 g of the title compound as a white powder, melting at 213°-223° C. was heated The mixture was then cooled the solvent was removed by distillation under reduced pressure The residue was then dissolved in 15 ml of acetonitrile dissolved in the solution the resulting reaction mixture was heated in a sealed tube at 80° C. for 18 hours It was then cooled the reaction mixture was evaporated to dryness The crude substance obtained from the fraction eluted with a 60:35:5 by volume mixture of methylene chloride, methanol and water was further purified by chromatography through two silica gel Lobar B columns The fraction eluted with the same solvent system

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution containing 1.275 g of dl-trans-2-hexadecyloxymethyl-3-hydroxytetrahydrofuran (prepared as described in Preparation 14), 1.060 g of 2-chloro-2-oxo-1,3,2-dioxaphospholane and 1.30 ml of diisopropylethylamine in 20 ml of 1,2-dichloroethane was heated, with stirring, at 80° C. for 16 hours. The mixture was then cooled, and the solvent was removed by distillation under reduced pressure. The residue was then dissolved in 15 ml of acetonitrile. 3.0 g of trimethylamine gas were passed through and dissolved in the solution, and the resulting reaction mixture was heated in a sealed tube at 80° C. for 18 hours. It was then cooled, and the reaction mixture was evaporated to dryness. The residue was subjected to column chromatography using 50 g of silica gel. The crude substance obtained from the fraction eluted with a 60:35:5 by volume mixture of methylene chloride, methanol and water was further purified by chromatography through two silica gel Lobar B columns. The fraction eluted with the same solvent system as described above gave 1.257 g of the title compound as a white powder, melting at 213°-223° C. was heated The mixture was then cooled the solvent was removed by distillation under reduced pressure The residue was then dissolved in 15 ml of acetonitrile dissolved in the solution the resulting reaction mixture was heated in a sealed tube at 80° C. for 18 hours It was then cooled the reaction mixture was evaporated to dryness The crude substance obtained from the fraction eluted with a 60:35:5 by volume mixture of methylene chloride, methanol and water was further purified by chromatography through two silica gel Lobar B columns The fraction eluted with the same solvent system

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Hydroxyethyl acrylate (11.5 ml, 0.1M) and triethylamine (14.6 ml) in dry diethyl ether (250 ml) were cooled to -25° C. under nitrogen as a solution of 2-chloro-2-oxo-1,3,2-dioxaphospholane (14.3 g) in dry diethyl ether was added over 20 minutes. The mixture was stirred for a further 1 hour at -20° C. and then allowed to warm to 10° C. over a further hour. The precipitate was filtered, washed with ethyl acetate (100 ml) and the combined filtrate and washings evaporated under reduced pressure to give a pale yellow oil (21 g). was added over 20 minutes to warm to 10° C. over a further hour The precipitate was filtered washed with ethyl acetate (100 ml) the combined filtrate and washings evaporated 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 freshly prepared 2-chloro-2-oxo-1,3,2-dioxaphospholane (14.2 g, 0.1M) in dry dichloromethane (30 ml) was added, drop-wise, to a stirred mixture of 2-(tert-butyldimethylsilyloxy)ethanol (17.6 g, 0.1M), triethylamine (18.1 ml), 0.13M) in dry dichloromethane (30 ml) at 0° C. under a nitrogen atmosphere. The mixture was allowed to warm to ambient temperature and was stirred for a further 2 hours. The mixture was filtered and the filtrand washed with n-hexane. The filtrate was evaporated in vacuo, diluted with n-hexane (30 ml) filtered and the filtrate evaporated in vacuo to give a brown oil. The mixture was filtered the filtrand washed with n-hexane The filtrate was evaporated in vacuo diluted with n-hexane (30 ml) filtered the filtrate evaporated in vacuo to give a brown oil

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

実験手順: A solution of freshly prepared 2-chloro-2-oxo-1,3,2-dioxaphospholane (14.2 g, 0.1M) in dry dichloromethane (30 ml) was added, drop-wise, to a stirred mixture of 2-(tert-butyldimethylsilyloxy)ethanol (17.6 g, 0.1M), triethylamine (18.1 ml, 0.13M) in dry dichloromethane (30 ml) at 0° C. under a nitrogen atmosphere. The mixture was allowed to warm to ambient temperature and was stirred for a further 2 hours. The mixture was filtered and the filtrand washed with n-hexane. The filtrate was evaporated in vacuo, diluted with n-hexane (30 ml) filtered and the filtrate evaporated in vacuo to give a brown oil. The mixture was filtered the filtrand washed with n-hexane The filtrate was evaporated in vacuo diluted with n-hexane (30 ml) filtered the filtrate evaporated in vacuo to give a brown oil