1-cyclohexyl-3-dimethoxyphosphorylpropan-2-one

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 49.6 g (0.40 mole) dimethyl methylphosphonate (Aldrich) in 500 ml dry tetrahydrofuran was cooled to -78° in a dry nitrogen atmosphere. To the stirred phosphonate solution was added 188 ml of 2.34 M n-butyllithium in hexane solution (Alfa Inorganics, Inc.) dropwise over a period of 40 minutes at such a rate that the reaction temperature never rose above -65°. After an additional 5 minutes stirring at -78°, 31.2 g (0.20 mole) methylcyclohexylacetate was added dropwise at a rate that kept the reaction temperature less than -70° (20 minutes). After 1.0 hour at -78° the reaction mixture was allowed to warm to ambient temperature, neutralized with 25 ml acetic acid and rotary evaporated to a white gel. The gelatenous material was taken up in 75 ml water, the aqueous phase extracted with 100 ml portions of chloroform (3x), the combined organic extracts were backwashed (50 cc H 2 O), dried (MgSO4), and concentrated (water aspirator) to a crude residue and distilled, b.p. 160°-162° (0.2 mm) to give dimethyl 2-oxo-3-cyclohexylpropylphosphonate (2h). the reaction temperature less than -70° (20 minutes) After 1.0 hour at -78° the reaction mixture was allowed rotary evaporated to a white gel the aqueous phase extracted with 100 ml portions of chloroform (3x) dried (MgSO4) concentrated (water aspirator) to a crude residue distilled

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 49.6 g (0.40 mole) dimethyl methylphosphonate (Aldrich) in 500 ml dry tetrahydrofuran was cooled to -78° in a dry nitrogen atmosphere. To the stirred phosphonate solution was added 188 ml of 2.34 M n-butyllithium in hexane solution (Alfa Inorganics, Inc.) dropwise over a period of 40 minutes at such a rate that the reaction temperature never rose above -65°. After an additional 5 minutes stirring at -78°, 31.2 g (0.20 mole) methylcyclohexylacetate was added dropwise at a rate that kept the reaction temperature less than -70° (20 minutes). After 1.0 hour at -78° the reaction mixture was allowed to warm to ambient temperature, neutralized with 25 ml acetic acid and rotary evaporated to a white gel. The gelatenous material was taken up in 75 ml water, the aqueous phase extracted with 100 ml portions of chloroform (3x), the combined organic extracts were backwashed (50 cc H 2 O), dried (MgSO4), and concentrated (water aspirator) to a crude residue and distilled, b.p. 160°-162° (0.2 mm) to give dimethyl 2-oxo-3-cyclohexylpropylphosphonate (2h). the reaction temperature less than -70° (20 minutes) After 1.0 hour at -78° the reaction mixture was allowed rotary evaporated to a white gel the aqueous phase extracted with 100 ml portions of chloroform (3x) dried (MgSO4) concentrated (water aspirator) to a crude residue distilled

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of dimethyl methylphosphonate (10.3 g, 0.083 mol) in 150 ml of anhydrous THF at -78° C. was added dropwise a solution of n-butyl lithium in hexane (1.67N, 50 ml, 0.083 mol) under argon atmosphere. After 30 minutes, a solution of methyl cyclohexylacetate (5.0 g, 0.035 mol) in 10 ml of anhydrous THF was further added and the mixture was stirred for 30 minutes. The reaction solution was allowed to warm to 0° C., diluted with 5 ml of acetic acid and 10 ml of water, and concentrated. 30 ml of water was added to the residue, and then 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 3-cyclohexyl-2-oxopropylphosphonate (7.4 g, 0.0298 mol, yield 85.3%, b.p. 118°-122° C./0.23 mmHg), which was assigned the structure by the following data: 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

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 49.6 g (0.40 mole) dimethyl methylphosphonate (Aldrich) in 500 ml dry tetrahydrofuran was cooled to -78° in a dry nitrogen atmosphere. To the stirred phosphonate solution was added 188 ml of 2.34 M n-butyllithium in hexane solution (Alfa Inorganics, Inc.) dropwise over a period of 40 minutes at such a rate that the reaction temperature never rose above -65°. After an additional 5 minutes stirring at -78°, 31.2 g (0.20 mole) methylcyclohexylacetate was added dropwise at a rate that kept the reaction temperature less than -70° (20 minutes). After 1.0 hour at -78° the reaction mixture was allowed to warm to ambient temperature, neutralized with 25 ml acetic acid and rotary evaporated to a white gel. The gelatenous material was taken up in 75 ml water, the aqueous phase extracted with 100 ml portions of chloroform (3x), the combined organic extracts were backwashed (50 cc H 2 O), dried (MgSO4), and concentrated (water aspirator) to a crude residue and distilled, b.p. 160°-162° (0.2 mm) to give dimethyl 2-oxo-3-cyclohexylpropylphosphonate (2h). the reaction temperature less than -70° (20 minutes) After 1.0 hour at -78° the reaction mixture was allowed rotary evaporated to a white gel the aqueous phase extracted with 100 ml portions of chloroform (3x) dried (MgSO4) concentrated (water aspirator) to a crude residue distilled

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of dimethyl methylphosphonate (10.3 g, 0.083 mol) in 150 ml of anhydrous THF at -78° C. was added dropwise a solution of n-butyl lithium in hexane (1.67N, 50 ml, 0.083 mol) under argon atmosphere. After 30 minutes, a solution of methyl cyclohexylacetate (5.0 g, 0.035 mol) in 10 ml of anhydrous THF was further added and the mixture was stirred for 30 minutes. The reaction solution was allowed to warm to 0° C., diluted with 5 ml of acetic acid and 10 ml of water, and concentrated. 30 ml of water was added to the residue, and then 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 3-cyclohexyl-2-oxopropylphosphonate (7.4 g, 0.0298 mol, yield 85.3%, b.p. 118°-122° C./0.23 mmHg), which was assigned the structure by the following data: 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

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 49.6 g (0.40 mole) dimethyl methylphosphonate (Aldrich) in 500 ml dry tetrahydrofuran was cooled to -78° in a dry nitrogen atmosphere. To the stirred phosphonate solution was added 188 ml of 2.34 M n-butyllithium in hexane solution (Alfa Inorganics, Inc.) dropwise over a period of 40 minutes at such a rate that the reaction temperature never rose above -65°. After an additional 5 minutes stirring at -78°, 31.2 g (0.20 mole) methylcyclohexylacetate was added dropwise at a rate that kept the reaction temperature less than -70° (20 minutes). After 1.0 hour at -78° the reaction mixture was allowed to warm to ambient temperature, neutralized with 25 ml acetic acid and rotary evaporated to a white gel. The gelatenous material was taken up in 75 ml water, the aqueous phase extracted with 100 ml portions of chloroform (3x), the combined organic extracts were backwashed (50 cc H 2 O), dried (MgSO4), and concentrated (water aspirator) to a crude residue and distilled, b.p. 160°-162° (0.2 mm) to give dimethyl 2-oxo-3-cyclohexylpropylphosphonate (2h). the reaction temperature less than -70° (20 minutes) After 1.0 hour at -78° the reaction mixture was allowed rotary evaporated to a white gel the aqueous phase extracted with 100 ml portions of chloroform (3x) dried (MgSO4) concentrated (water aspirator) to a crude residue distilled