1-cyclohexyl-2-dimethoxyphosphorylethanone

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 dimethyl 2-cyclohexyl-2-oxoethylphosphonate (10.1 g.) in dry tetrahydrofuran (40 ml.) was added to a stirred suspension of sodium hydride (1.04 g.) in dry tetrahydrofuran (300 ml.). The mixture was stirred at room temperature until the evolution of hydrogen had ceased, then treated dropwise with a solution of 7-formyl-6-(7-hydroxyheptyl)-1,4-dioxaspiro[4,4]nonane [10.2 g; prepared as described in Example 1(iv) above] in dry tetrahydrofuran (100 ml.) and stirred for a further 2 hours. The mixture was acidified to pH 4 by the addition of glacial acetic acid, the solvents were removed in vacuo, the residue was triturated with diethyl ether and the solid filtered off. The ethereal solution was washed with aqueous sodium carbonate solution, dried over magnesium sulphate, and evaporated to dryness, to give 7-(3-cyclohexyl-3-oxoprop-1-enyl)-6-(7-hydroxyheptyl)-1,4-dioxaspiro[4,4]nonane (16 g.), νmax 3400 cm-1, 1680 cm-1, 1650 cm-1, 1620 cm-1, 1040 cm-1. the solvents were removed in vacuo the residue was triturated with diethyl ether the solid filtered off The ethereal solution was washed with aqueous sodium carbonate solution dried over magnesium sulphate evaporated to dryness

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

実験手順: To a stirred solution of dimethyl methylphosphonate (11.73 g, 0.095 mol) in 150 ml of anhydrous THF at -78° C. was added dropwise a solution of n-butyl lithium in hexane (1.67N, 56.7 ml, 0.095 mol) under argon atmosphere, and the mixture was stirred for 30 minutes. To this reaction mixture was added dropwise a solution of methyl cyclohexanecarboxylate (5.6 g, 0.0394 mol) in 10 ml of anhydrous THF. After being stirred for 30 minutes, the reaction mixture was allowed to warm to 0° C., diluted with 5.5 ml of acetic acid and 10 ml of water, and concentrated. 30 ml of water was added to the residue, and the mixture was extracted with ethyl acetate (50 ml×2). The combined ethyl acetate layers were washed with water (20 ml×1) and brine (20 ml×1), dried over anhydrous sodium sulfate, and concentrated. The residue was distilled under reduced pressure to give a colorless transparent oil of dimethyl 2-cyclohexyl-2-oxo-ethylphosphonate (8.62 g, 0.037 mol, yield 93.4%, b.p. 114°-115° C./0.25 mmHg), which was assigned the structure by the following data: After being stirred for 30 minutes concentrated 30 ml of water was added to the residue the mixture was extracted with ethyl acetate (50 ml×2) The combined ethyl acetate layers were washed with water (20 ml×1) and brine (20 ml×1) dried over anhydrous sodium sulfate concentrated The residue was distilled under reduced pressure

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

実験手順: Dimethyl(2-cyclohexyl-2-oxoethyl)phosphonate (3.3 g) was added to a stirred suspension of sodium hydride (0.34 g) and 1,4,7,10,13,16-hexaoxacyclooctadecane (10 mg) in dry tetrahydrofuran (90 ml) in an atmosphere of argon and the mixture was stirred for 12 hours. The mixture was then cooled to 0° C. and treated dropwise with 6-acetoxy-2-formylbicyclo[3,3,0]octane (1.05 g; prepared as described in Reference Example 21 and predominantly in the 2β-configuration). The reaction mixture was allowed to warm to room temperature and then it was stirred for a further period of 24 hours. A solution of glacial acetic acid (400 mg) in diethyl ether (1 ml) was then added and the mixture was concentrated in vacuo. The residue was dissolved in ethyl acetate (10 ml) and the resulting solution was washed with water (10 ml) and then with saturated aqueous sodium chloride solution (10 ml), dried over magnesium sulphate, and concentrated in vacuo. The resulting oil was treated with acetic anhydride (1 ml) and pyridine (4 ml) at 20° C. and left to stand for 12 hours. Concentration at 0.01 mmHg gave an oil, which was subjected to chromatography on a silica gel column, eluting with mixtures of ethyl acetate and hexane (1:6 v/v and then 1:1 v/v), to give (E)- 6-acetoxy-2-(3-cyclohexyl-3-oxoprop-1-enyl)bicyclo[3,3,0]octane (0.84 g), predominantly in the 2β-configuration. prepared to warm to room temperature it was stirred for a further period of 24 hours the mixture was concentrated in vacuo The residue was dissolved in ethyl acetate (10 ml) the resulting solution was washed with water (10 ml) with saturated aqueous sodium chloride solution (10 ml), dried over magnesium sulphate concentrated in vacuo The resulting oil was treated with acetic anhydride (1 ml) and pyridine (4 ml) at 20° C. left to stand for 12 hours Concentration at 0.01 mmHg gave an oil, which eluting with mixtures of ethyl acetate and hexane (1:6 v/v

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

実験手順: A solution of dimethyl 2-cyclohexyl-2-oxoethylphosphonate (10.1 g.) in dry tetrahydrofuran (40 ml.) was added to a stirred suspension of sodium hydride (1.04 g.) in dry tetrahydrofuran (300 ml.). The mixture was stirred at room temperature until the evolution of hydrogen had ceased, then treated dropwise with a solution of 7-formyl-6-(7-hydroxyheptyl)-1,4-dioxaspiro[4,4]nonane [10.2 g; prepared as described in Example 1(iv) above] in dry tetrahydrofuran (100 ml.) and stirred for a further 2 hours. The mixture was acidified to pH 4 by the addition of glacial acetic acid, the solvents were removed in vacuo, the residue was triturated with diethyl ether and the solid filtered off. The ethereal solution was washed with aqueous sodium carbonate solution, dried over magnesium sulphate, and evaporated to dryness, to give 7-(3-cyclohexyl-3-oxoprop-1-enyl)-6-(7-hydroxyheptyl)-1,4-dioxaspiro[4,4]nonane (16 g.), νmax 3400 cm-1, 1680 cm-1, 1650 cm-1, 1620 cm-1, 1040 cm-1. the solvents were removed in vacuo the residue was triturated with diethyl ether the solid filtered off The ethereal solution was washed with aqueous sodium carbonate solution dried over magnesium sulphate evaporated to dryness

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

実験手順: A solution of dimethyl 2-cyclohexyl-2-oxoethylphosphonate (10.1 g.) in dry tetrahydrofuran (40 ml.) was added to a stirred suspension of sodium hydride (1.04 g.) in dry tetrahydrofuran (300 ml.). The mixture was stirred at room temperature until the evolution of hydrogen had ceased, then treated dropwise with a solution of 7-formyl-6-(7-hydroxyheptyl)-1,4-dioxaspiro[4,4]nonane [10.2 g; prepared as described in Example 1(iv) above] in dry tetrahydrofuran (100 ml.) and stirred for a further 2 hours. The mixture was acidified to pH 4 by the addition of glacial acetic acid, the solvents were removed in vacuo, the residue was triturated with diethyl ether and the solid filtered off. The ethereal solution was washed with aqueous sodium carbonate solution, dried over magnesium sulphate, and evaporated to dryness, to give 7-(3-cyclohexyl-3-oxoprop-1-enyl)-6-(7-hydroxyheptyl)-1,4-dioxaspiro[4,4]nonane (16 g.), νmax 3400 cm-1, 1680 cm-1, 1650 cm-1, 1620 cm-1, 1040 cm-1. the solvents were removed in vacuo the residue was triturated with diethyl ether the solid filtered off The ethereal solution was washed with aqueous sodium carbonate solution dried over magnesium sulphate evaporated to dryness

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 dimethyl 2-cyclohexyl-2-oxoethylphosphonate (10.1 g.) in dry tetrahydrofuran (40 ml.) was added to a stirred suspension of sodium hydride (1.04 g.) in dry tetrahydrofuran (300 ml.). The mixture was stirred at room temperature until the evolution of hydrogen had ceased, then treated dropwise with a solution of 7-formyl-6-(7-hydroxyheptyl)-1,4-dioxaspiro[4,4]nonane [10.2 g; prepared as described in Example 1(iv) above] in dry tetrahydrofuran (100 ml.) and stirred for a further 2 hours. The mixture was acidified to pH 4 by the addition of glacial acetic acid, the solvents were removed in vacuo, the residue was triturated with diethyl ether and the solid filtered off. The ethereal solution was washed with aqueous sodium carbonate solution, dried over magnesium sulphate, and evaporated to dryness, to give 7-(3-cyclohexyl-3-oxoprop-1-enyl)-6-(7-hydroxyheptyl)-1,4-dioxaspiro[4,4]nonane (16 g.), νmax 3400 cm-1, 1680 cm-1, 1650 cm-1, 1620 cm-1, 1040 cm-1. the solvents were removed in vacuo the residue was triturated with diethyl ether the solid filtered off The ethereal solution was washed with aqueous sodium carbonate solution dried over magnesium sulphate evaporated to dryness

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

実験手順: A solution of dimethyl 2-cyclohexyl-2-oxoethylphosphonate (10.1 g.) in dry tetrahydrofuran (40 ml.) was added to a stirred suspension of sodium hydride (1.04 g.) in dry tetrahydrofuran (300 ml.). The mixture was stirred at room temperature until the evolution of hydrogen had ceased, then treated dropwise with a solution of 7-formyl-6-(7-hydroxyheptyl)-1,4-dioxaspiro[4,4]nonane [10.2 g; prepared as described in Example 1(iv) above] in dry tetrahydrofuran (100 ml.) and stirred for a further 2 hours. The mixture was acidified to pH 4 by the addition of glacial acetic acid, the solvents were removed in vacuo, the residue was triturated with diethyl ether and the solid filtered off. The ethereal solution was washed with aqueous sodium carbonate solution, dried over magnesium sulphate, and evaporated to dryness, to give 7-(3-cyclohexyl-3-oxoprop-1-enyl)-6-(7-hydroxyheptyl)-1,4-dioxaspiro[4,4]nonane (16 g.), νmax 3400 cm-1, 1680 cm-1, 1650 cm-1, 1620 cm-1, 1040 cm-1. the solvents were removed in vacuo the residue was triturated with diethyl ether the solid filtered off The ethereal solution was washed with aqueous sodium carbonate solution dried over magnesium sulphate evaporated to dryness

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

実験手順: To a stirred solution of dimethyl methylphosphonate (11.73 g, 0.095 mol) in 150 ml of anhydrous THF at -78° C. was added dropwise a solution of n-butyl lithium in hexane (1.67N, 56.7 ml, 0.095 mol) under argon atmosphere, and the mixture was stirred for 30 minutes. To this reaction mixture was added dropwise a solution of methyl cyclohexanecarboxylate (5.6 g, 0.0394 mol) in 10 ml of anhydrous THF. After being stirred for 30 minutes, the reaction mixture was allowed to warm to 0° C., diluted with 5.5 ml of acetic acid and 10 ml of water, and concentrated. 30 ml of water was added to the residue, and the mixture was extracted with ethyl acetate (50 ml×2). The combined ethyl acetate layers were washed with water (20 ml×1) and brine (20 ml×1), dried over anhydrous sodium sulfate, and concentrated. The residue was distilled under reduced pressure to give a colorless transparent oil of dimethyl 2-cyclohexyl-2-oxo-ethylphosphonate (8.62 g, 0.037 mol, yield 93.4%, b.p. 114°-115° C./0.25 mmHg), which was assigned the structure by the following data: After being stirred for 30 minutes concentrated 30 ml of water was added to the residue the mixture was extracted with ethyl acetate (50 ml×2) The combined ethyl acetate layers were washed with water (20 ml×1) and brine (20 ml×1) dried over anhydrous sodium sulfate concentrated The residue was distilled under reduced pressure

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

実験手順: Dimethyl(2-cyclohexyl-2-oxoethyl)phosphonate (3.3 g) was added to a stirred suspension of sodium hydride (0.34 g) and 1,4,7,10,13,16-hexaoxacyclooctadecane (10 mg) in dry tetrahydrofuran (90 ml) in an atmosphere of argon and the mixture was stirred for 12 hours. The mixture was then cooled to 0° C. and treated dropwise with 6-acetoxy-2-formylbicyclo[3,3,0]octane (1.05 g; prepared as described in Reference Example 21 and predominantly in the 2β-configuration). The reaction mixture was allowed to warm to room temperature and then it was stirred for a further period of 24 hours. A solution of glacial acetic acid (400 mg) in diethyl ether (1 ml) was then added and the mixture was concentrated in vacuo. The residue was dissolved in ethyl acetate (10 ml) and the resulting solution was washed with water (10 ml) and then with saturated aqueous sodium chloride solution (10 ml), dried over magnesium sulphate, and concentrated in vacuo. The resulting oil was treated with acetic anhydride (1 ml) and pyridine (4 ml) at 20° C. and left to stand for 12 hours. Concentration at 0.01 mmHg gave an oil, which was subjected to chromatography on a silica gel column, eluting with mixtures of ethyl acetate and hexane (1:6 v/v and then 1:1 v/v), to give (E)- 6-acetoxy-2-(3-cyclohexyl-3-oxoprop-1-enyl)bicyclo[3,3,0]octane (0.84 g), predominantly in the 2β-configuration. prepared to warm to room temperature it was stirred for a further period of 24 hours the mixture was concentrated in vacuo The residue was dissolved in ethyl acetate (10 ml) the resulting solution was washed with water (10 ml) with saturated aqueous sodium chloride solution (10 ml), dried over magnesium sulphate concentrated in vacuo The resulting oil was treated with acetic anhydride (1 ml) and pyridine (4 ml) at 20° C. left to stand for 12 hours Concentration at 0.01 mmHg gave an oil, which eluting with mixtures of ethyl acetate and hexane (1:6 v/v

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

実験手順: A solution of dimethyl 2-cyclohexyl-2-oxoethylphosphonate (10.1 g.) in dry tetrahydrofuran (40 ml.) was added to a stirred suspension of sodium hydride (1.04 g.) in dry tetrahydrofuran (300 ml.). The mixture was stirred at room temperature until the evolution of hydrogen had ceased, then treated dropwise with a solution of 7-formyl-6-(7-hydroxyheptyl)-1,4-dioxaspiro[4,4]nonane [10.2 g; prepared as described in Example 1(iv) above] in dry tetrahydrofuran (100 ml.) and stirred for a further 2 hours. The mixture was acidified to pH 4 by the addition of glacial acetic acid, the solvents were removed in vacuo, the residue was triturated with diethyl ether and the solid filtered off. The ethereal solution was washed with aqueous sodium carbonate solution, dried over magnesium sulphate, and evaporated to dryness, to give 7-(3-cyclohexyl-3-oxoprop-1-enyl)-6-(7-hydroxyheptyl)-1,4-dioxaspiro[4,4]nonane (16 g.), νmax 3400 cm-1, 1680 cm-1, 1650 cm-1, 1620 cm-1, 1040 cm-1. the solvents were removed in vacuo the residue was triturated with diethyl ether the solid filtered off The ethereal solution was washed with aqueous sodium carbonate solution dried over magnesium sulphate evaporated to dryness