ethyl 4-diethoxyphosphoryl-3-methylbut-2-enoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 30.3 g. of sodium ethoxide in 300 ml. of tetrahydrofuran was added 118 g. of diethyl 3-ethoxycarbonyl-2-methyl-2-propenylphosphonate. To the mixture was added 67 g. of 3,7,11-trimethyl-2,4,6,10-dodecatetraene-1-al under stirring, chilling with ice and shielding from the light. After 1 hour, the reaction liquid was poured into 1 liter of water, and 1 liter of n-hexane was added for extraction. The n-hexane phase was separated, washed with two 100 ml. portions of a mixture of methanol and water (2:1), and concentrated to give 99 g. of a concentrate. To a refluxing solution of 8.2 g. of potassium hydroxide and 80 ml. of isopropyl alcohol was added 21 g. of the concentrate under shielding from the light. After 15 minutes, the reaction liquid was poured into 300 ml. of ice-water, made acidic by addition of hydrochloric acid, and extracted with 300 ml. of diethyl ether. The extract was washed with three 100 ml. portions of water, dried over magnesium sulfate, and evaporated to remove the solvent. The residue was dissolved in 200 ml. of n-hexane and chilled to -20° C. to crystallize it. There was obtained 9.8 g. of the desired product as pale yellow crystals. To a suspension of 30.3 g To the mixture was added 67 g chilling with ice and shielding from the light the reaction liquid was added for extraction The n-hexane phase was separated washed with two 100 ml portions of a mixture of methanol and water (2:1) concentrated to give 99 g of the concentrate After 15 minutes the reaction liquid was poured into 300 ml extracted with 300 ml The extract was washed with three 100 ml portions of water, dried over magnesium sulfate evaporated to remove the solvent The residue was dissolved in 200 ml to crystallize it There was obtained 9.8 g

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 30.0 g of sodium ethoxide in 300 ml. of tetrahydrofuran was added 118 g. of diethyl 3-ethoxycarbonyl-2-methyl-2-propenylphosphonate. To the mixture was added 67 g. of 3,7,11-trimethyl-2,4,6,10-dodecatetraen-1-al under stirring, chilling with ice and shielding from the light. After 1 hour, the reaction liquid was poured into 1 liter of water, and 1 liter of n-hexane was added for extraction. The n-hexane phase was separated, washed with two 100 ml. portions of a mixture of methanol and water (2:1), and concentrated to give 99 g. of a concentrate. To a refluxing solution of 8.2 g. of potassium hydroxide and 80 ml. of ispropyl alcohol was added 21 g. of the concentrate under shielding from the light. After 15 minutes, the reaction liquid was poured into 300 ml. of ice-water, made acidic by addition of hydrochloric acid, and extracted with 300 ml. of diethyl ether. The extract was washed with three 100 ml. portions of water, dried over magnesium sulfate, and evaporated to remove the solvent. The residue was dissolved in 200 ml. of n-hexane and chilled to -20° C. to crystallize. There was obtained 9.8 g. of the desired product as pale yellow crystals. To the mixture was added 67 g chilling with ice and shielding from the light the reaction liquid was added for extraction The n-hexane phase was separated washed with two 100 ml portions of a mixture of methanol and water (2:1) concentrated to give 99 g of the concentrate After 15 minutes the reaction liquid was poured into 300 ml extracted with 300 ml The extract was washed with three 100 ml portions of water, dried over magnesium sulfate evaporated to remove the solvent The residue was dissolved in 200 ml to crystallize There was obtained 9.8 g

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 30.0 g of sodium ethoxide in 300 ml. of tetrahydrofuran was added 118 g. of diethyl 3-ethoxycarbonyl-2-methyl-2-propenylphosphonate. To the mixture was added 67 g. of 3,7,11-trimethyl-2,4,6,10-dodecatetraen-1-al under stirring, chilling with ice and shielding from the light. After 1 hour, the reaction liquid was poured into 1 liter of water, and 1 liter of n-hexane was added for extraction. The n-hexane phase was separated, washed with two 100 ml. portions of a mixture of methanol and water (2:1), and concentrated to give 99 g. of a concentrate. To a refluxing solution of 8.2 g. of potassium hydroxide and 80 ml. of ispropyl alcohol was added 21 g. of the concentrate under shielding from the light. After 15 minutes, the reaction liquid was poured into 300 ml. of ice-water, made acidic by addition of hydrochloric acid, and extracted with 300 ml. of diethyl ether. The extract was washed with three 100 ml. portions of water, dried over magnesium sulfate, and evaporated to remove the solvent. The residue was dissolved in 200 ml. of n-hexane and chilled to -20° C. to crystallize. There was obtained 9.8 g. of the desired product as pale yellow crystals. To the mixture was added 67 g chilling with ice and shielding from the light the reaction liquid was added for extraction The n-hexane phase was separated washed with two 100 ml portions of a mixture of methanol and water (2:1) concentrated to give 99 g of the concentrate After 15 minutes the reaction liquid was poured into 300 ml extracted with 300 ml The extract was washed with three 100 ml portions of water, dried over magnesium sulfate evaporated to remove the solvent The residue was dissolved in 200 ml to crystallize There was obtained 9.8 g

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 2.03 g of NaH (50% in mineral oil) was suspended in 120 ml of DMF. 12.9 g of 4-(diethoxy-phosphinyl)-3-methyl-but-2-enoic acid ethyl ester was added at 0°. The mixture was stirred for 15 min at 0° and for 30 min at RT. After recooling to 0°, 5.72 g of 2-bromo-cyclopent-1-enecarbaldehyde, dissolved in 11 ml of DMF, was added drop by drop and allowed to react for 10 min. at 0° and for 2 h at RT. The mixture was then poured onto crushed ice, extracted with EtOEt, washed with sat. NaCi-solution, dried over Na2SO4, and evaporated to dryness. Purification of the residue by flash chromatography (silica gel, hexane/AcOEt=97/3) and crystallization from hexane/trace amounts of AcOEt yielded finally 3.408 g of pure (2E,4E)-5-(2-bromo-cyclopent-1-enyl)-3-methyl-penta-2,4-dienoic acid ethyl ester as yellowish crystals of mp. 85°-86°. After recooling to 0° was added drop by drop to react for 10 min. at 0° and for 2 h at RT The mixture was then poured onto crushed ice extracted with EtOEt washed with sat. NaCi-solution dried over Na2SO4 evaporated to dryness Purification of the residue by flash chromatography (silica gel, hexane/AcOEt=97/3) and crystallization from hexane/

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

Procedure: Following General Procedure I-1, ethyl 4(diethoxyphosphoryl)-3-methyl-but-2-enoate (645 mg, 2.44 mmol) and (2E)-3-(4-Bromo-8-sec-butyl-3-ethoxy-5,5-dimethyl-5,6-dihydro-naphthalen-2-yl)-2-fluoro-pent-2-enal (Compound A-154, 333 mg, 0.81 mmol) were reacted to give the title compound as a light yellow syrup after purification by column chromatography (silica gel, 2% ethyl acetate in hexane). were reacted

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

Procedure: To a solution of 4-(diethoxy-phosphoryl)-3-methyl-but-2-enoic acid ethyl ester (10.6 mL, 43.6 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU, 20 mL) and THF (80 mL) at −78° C. was added n-BuLi dropwise (1.6 M in hexanes, 27.2 mL, 43.6 mmol). After 10 min, 3-(3,5-diisopropyl-2-propoxy-phenyl)-pent-2-enal (Intermediate 6, 8.77 g, 29.0 mmol) in THF (15 mL and 5 mL rinse) was added slowly to the reaction. The mixture was stirred at −78° C. for 2h, was quenched with saturated NH4Cl and extracted with EtOAc. The organic layer was separated, washed successively with H2O, brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (2.5% EtOAc-hexanes) to yield the title compound as a yellow syrup (11.4 g, 95%). was quenched with saturated NH4Cl extracted with EtOAc The organic layer was separated washed successively with H2O, brine dried over Na2SO4 concentrated in vacuo The residue was purified by flash column chromatography on silica gel (2.5% EtOAc-hexanes)

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 30.3 g. of sodium ethoxide in 300 ml. of tetrahydrofuran was added 118 g. of diethyl 3-ethoxycarbonyl-2-methyl-2-propenylphosphonate. To the mixture was added 67 g. of 3,7,11-trimethyl-2,4,6,10-dodecatetraene-1-ol under stirring, chilling with ice and shielding from the light. After 1 hour, the reaction liquid was poured into 1 liter of water, and 1 liter of n-hexane was added for extraction. The n-hexane phase was separated, washed with two 100 ml. portions of a mixture of methanoland water (2:1), and concentrated to give 99 g. ofa concentrate. To a refluxing solution of 8.2 g. of potassium hydroxide and 80 ml. of isopropyl alcohol was added 21 g. of the concentrate under shielding from the light. After 15 minutes, the reaction liquid was poured into 300 ml. of ice-water, made acidic by addition of hydrochloric acid, and extracted with 300 ml. of diethyl ether. The extract was washed with three 100 ml. portions of water, dried over magnesium sulfate, and evaporated to remove the solvent. The residue was dissolved in 200 ml. of n-hexane and chilled to -20° C. to crystallize it. There was obtained 9.8 g. of the desired product as pale yellow crystals. To a suspension of 30.3 g To the mixture was added 67 g chilling with ice and shielding from the light the reaction liquid was added for extraction The n-hexane phase was separated washed with two 100 ml portions of a mixture of methanoland water (2:1) concentrated to give 99 g ofa concentrate of isopropyl alcohol was added 21 g of the concentrate After 15 minutes the reaction liquid was poured into 300 ml extracted with 300 ml The extract was washed with three 100 ml portions of water, dried over magnesium sulfate evaporated to remove the solvent The residue was dissolved in 200 ml to crystallize it There was obtained 9.8 g