Diethyl (4-carbethoxybenzyl)phosphonate

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

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

Procedure: 193 mg of NaH (55% in mineral oil) were placed in 10 ml of abs. DMF under argon and 1.66 g of diethyl (4-carbethoxybenzyl)-phosphonate were added thereto at 0° and the mixture was subsequently stirred at room temperature until the H2 evolution had finished. Then, 1.08 g of 2-formyl-3-pent-2-ynyloxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalene without addition solvent were added at 0°. After 30 min. at room temperature the mixture was extracted with hexane and washed twice with ethanol/H2O=8/2. Drying, evaporation and direct crystallization from hexane yielded 1.45 g of ethyl (E)-4-[2-(3-pent-2-ynyloxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-vinyl]-benzoate as yellowish crystals of m.p. 80-82°. were added at 0° After 30 min. at room temperature the mixture was extracted with hexane washed twice with ethanol/H2O=8/2 Drying evaporation and direct crystallization from hexane

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

Procedure: 248 mg of NaH (about 50% in oil) were placed in 12 ml of abs. DMF under argon. 2.45 g of diethyl (4-carbethoxybenzyl)phosphonate were added thereto at 0° and the mixture was subsequently stirred at room temperature for about 2 hours until the H2 evolution had finished. The mixture was cooled to −10° C. and 2.20 g of (5RS,9SR,10RS)-10-t-butyldimethylsilyloxy-2-formyl-3-heptyloxy-5,9-dimethyl-6,7,8,9-tetrahydro-5,9-methano-5H-benzocycloheptene dissolved in 10 ml of abs. DMF were slowly added dropwise thereto. Then, the cooling bath was removed and the mixture was left to react at room temperature for 2 hours. It was then poured into ice/NH4Cl solution, extracted with diethyl ether, washed with NaCl solution, dried over Na2SO4 and concentrated. Flash chromatography on SiO2 (hexane/ethyl acetate 98/2) gave 2.32 g of ethyl (E)-4-[2-[(5RS,9SR,10RS)-10-t-butyldimethylsilyloxy-3-heptyloxy-5,9-dimethyl-6,7,8,9-tetrahydro-5,9-methano-5H-benzocyclohepten-2-yl]vinyl]benzoate as a yellowish oil. The mixture was cooled to −10° C. Then, the cooling bath was removed the mixture was left to react at room temperature for 2 hours extracted with diethyl ether washed with NaCl solution dried over Na2SO4 concentrated

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

Procedure: 1.3 g of sodium hydride, 50% in mineral oil, were suspended in 20 ml of abs. dimethyl sulphoxide (DMSO) and treated dropwise at 15° C. with a solution of 8.6 g of diethyl (4-carbethoxybenzyl)-phosphonate in 25 ml of abs. DMSO. The mixture was stirred at room temperature for 1 hour and then a solution of 3.3 g of the above aldehyde in 25 ml of abs. DMSO and 10 ml of tetrahydrofuran was added dropwise thereto. After stirring at 40° C. for 2 hours the mixture was poured into ice-water, acidified with 2N hydrochloric acid and extracted with ethyl acetate. After drying the organic phase with sodium sulphate and evaporation of the solvent the crude product was filtered over a silica gel column (eluent hexane/5% methyl tert.butyl ether). After recrystallization from hexane/ethyl acetate there were obtained 4.4 g of ethyl (E)-4-[2-(5,5,8,8-tetra-methyl-3-propoxy-5,6,7,8-tetrahydro-naphthalen-2-yl)vinyl]benzoate in the form of white crystals, melting point 97-100° C. After stirring at 40° C. for 2 hours the mixture extracted with ethyl acetate After drying the organic phase with sodium sulphate and evaporation of the solvent the crude product was filtered over a silica gel column (eluent hexane/5% methyl tert.butyl ether) After recrystallization from hexane/ethyl acetate there

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

Procedure: 8.85 g of ethyl α-(diethoxyphosphinyl)-p-toluate were slowly added dropwise to 1.3 g of sodium hydride (50% in mineral oil) in 28 ml of dimethylformamide. The reaction mixture was stirred at room temperature until the evolution of hydrogen has finished. Thereafter, 4.2 g of 2,3,4,5-tetrahydro-3,3-dimethyl-benzothiepin-7-yl methyl ketone were added and the reaction mixture was stirred at room temperature for 2 hours. Thereafter, the mixture was poured on to ice/sodium chloride, extracted with ether, the ethereal solution was washed with water and dried and evaporated. Chromatography on silica gel (petroleum ether/ethyl acetate (95:5)) and recrystallization from hexane yielded ethyl p-[(E)-2-(2,3,4,5-tetrahydro-3,3-dimethyl-1-benzothiepin-7-yl)propenyl]benzoate of melting point 96°-97° C. extracted with ether the ethereal solution was washed with water dried evaporated Chromatography on silica gel (petroleum ether/ethyl acetate (95:5)) and recrystallization from hexane

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

Procedure: 2.9 g of a 50% suspension of sodium hydride in mineral oil were suspended in 30 ml of dimethylformamide after two-fold washing with pentane and treated dropwise at room temperature with a solution of 17.3 g of diethyl (4-carbethoxybenzyl)phosphonate in 50 ml of dimethylformamide. After stirring at room temperature for 1 hour, a solution of 5 g of 1,2,3,4-tetrahydro-1,4,4-trimethyl-7-quinolinyl methyl ketone in 50 ml of dimethylformamide was added dropwise thereto. The reaction mixture was heated to 50° C. for 1 hour, poured on to ice/water and extracted with ethyl acetate. The brownish oil obtained after drying and evaporation of the organic phase was chromatographed (silica gel, eluting agent hexane/ethyl acetate=9:1) and gave 4.2 g of ethyl p-[2-(1,2,3,4-tetrahydro-1,4,4-trimethyl-7-quinolinyl)propenyl]benzoate as a slightly yellow, viscous oil. The reaction mixture was heated to 50° C. for 1 hour extracted with ethyl acetate The brownish oil obtained after drying evaporation of the organic phase was chromatographed (silica gel, eluting agent hexane/ethyl acetate=9:1)

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

Procedure: 0.5 g of a 50% suspension of sodium hydride in mineral oil were suspended in 15 ml of dimethyl sulfoxide and treated under argon with a solution of 3.2 g of diethyl (4-carbethoxybenzyl)phosphonate in 10 ml of dimethyl sulfoxide. The mixture was subsequently heated to 40' C. for 20 minutes, cooled to room temperature, a solution of 0.87 g of 3,4-dihydro-4,4-dimethyl-7-acetyl-2H-1-benzopyran in 5 ml of dimethyl sulfoxide was added dropwise thereto and the mixture was heated to 40° C. for 1 hour. The reaction mixture obtained was poured on to ice/water, acidified with 1N hydrochloric acid and extracted repeatedly with ether. The organic phase was washed with water, dried and evaporated. There was obtained a yellowish oil which, after filtration over a short column (silica gel, eluting agent hexane/ethyl acetate=9:1), crystallized from hexane and yielded 0.9 g of ethyl p-[2-(3,4-dihydro-4,4-dimethyl-2H-1-benzopyran-7-yl)propenyl]-benzoate, m.p. 49°-50° C. The mixture was subsequently heated to 40' C the mixture was heated to 40° C. for 1 hour The reaction mixture obtained extracted repeatedly with ether The organic phase was washed with water dried evaporated There was obtained a yellowish oil which after filtration over a short column (silica gel, eluting agent hexane/ethyl acetate=9:1) crystallized from hexane

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

Procedure: 85 mg of NaH (ca. 1.4 eq., 50% in mineral oil) was added to a solution of 534 mg (1.4 eq.) of 4-(diethoxyphosphorylmethyl)-benzoic acid ethyl ester in 1.9 ml of abs. DMF at 0° C. The mixture was stirred at 0° C. for 0.5 h and at room temperature for 1.5 h. After cooling to 0° C., 336 mg (1.27 mmol) of 5-ethoxymethyl-5-methyl-2,3,4,5-tetrahydrobenzo[b]thiepine-8-carbaldehyde, dissolved in 1 ml of DMF, was added and allowed to react for 2 h at room temperature. The mixture was then poured onto crushed ice, extracted twice with diethylether, the organic phase was washed with water, dried over magnesium sulfate, filtrated and evaporated to dryness. Purification of the residue by flash chromatography (silica gel, hexane/ethylacetate 95/5) afforded 409 mg of pure, colorless title compound. at 0° C After cooling to 0° C. was added to react for 2 h at room temperature The mixture was then poured onto crushed ice extracted twice with diethylether the organic phase was washed with water dried over magnesium sulfate filtrated evaporated to dryness Purification of the residue by flash chromatography (silica gel, hexane/ethylacetate 95/5)

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

Procedure: 193 mg of NaH (55% in mineral oil) were placed in 10 ml of abs. DMF under argon and 1.66 g of diethyl (4-carbethoxybenzyl)-phosphonate were added thereto at 0° and the mixture was subsequently stirred at room temperature until the H2 evolution had finished. Then, 1.08 g of 2-formyl-3-pent-2-ynyloxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalene without addition solvent were added at 0°. After 30 min. at room temperature the mixture was extracted with hexane and washed twice with ethanol/H2O=8/2. Drying, evaporation and direct crystallization from hexane yielded 1.45 g of ethyl (E)-4-[2-(3-pent-2-ynyloxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-vinyl]-benzoate as yellowish crystals of m.p. 80-82°. were added at 0° After 30 min. at room temperature the mixture was extracted with hexane washed twice with ethanol/H2O=8/2 Drying evaporation and direct crystallization from hexane

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

Procedure: 193 mg of NaH (55% in mineral oil) were placed in 10 ml of abs. DMF under argon and 1.66 g of diethyl (4-carbethoxybenzyl)-phosphonate were added thereto at 0° and the mixture was subsequently stirred at room temperature until the H2 evolution had finished. Then, 1.08 g of 2-formyl-3-pent-2-ynyloxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalene without addition solvent were added at 0°. After 30 min. at room temperature the mixture was extracted with hexane and washed twice with ethanol/H2O=8/2. Drying, evaporation and direct crystallization from hexane yielded 1.45 g of ethyl (E)-4-[2-(3-pent-2-ynyloxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-vinyl]-benzoate as yellowish crystals of m.p. 80-82°. were added at 0° After 30 min. at room temperature the mixture was extracted with hexane washed twice with ethanol/H2O=8/2 Drying evaporation and direct crystallization from hexane

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

Procedure: 248 mg of NaH (about 50% in oil) were placed in 12 ml of abs. DMF under argon. 2.45 g of diethyl (4-carbethoxybenzyl)phosphonate were added thereto at 0° and the mixture was subsequently stirred at room temperature for about 2 hours until the H2 evolution had finished. The mixture was cooled to −10° C. and 2.20 g of (5RS,9SR,10RS)-10-t-butyldimethylsilyloxy-2-formyl-3-heptyloxy-5,9-dimethyl-6,7,8,9-tetrahydro-5,9-methano-5H-benzocycloheptene dissolved in 10 ml of abs. DMF were slowly added dropwise thereto. Then, the cooling bath was removed and the mixture was left to react at room temperature for 2 hours. It was then poured into ice/NH4Cl solution, extracted with diethyl ether, washed with NaCl solution, dried over Na2SO4 and concentrated. Flash chromatography on SiO2 (hexane/ethyl acetate 98/2) gave 2.32 g of ethyl (E)-4-[2-[(5RS,9SR,10RS)-10-t-butyldimethylsilyloxy-3-heptyloxy-5,9-dimethyl-6,7,8,9-tetrahydro-5,9-methano-5H-benzocyclohepten-2-yl]vinyl]benzoate as a yellowish oil. The mixture was cooled to −10° C. Then, the cooling bath was removed the mixture was left to react at room temperature for 2 hours extracted with diethyl ether washed with NaCl solution dried over Na2SO4 concentrated

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

Procedure: 248 mg of NaH (about 50% in oil) were placed in 12 ml of abs. DMF under argon. 2.45 g of diethyl (4-carbethoxybenzyl)phosphonate were added thereto at 0° and the mixture was subsequently stirred at room temperature for about 2 hours until the H2 evolution had finished. The mixture was cooled to −10° C. and 2.20 g of (5RS,9SR,10RS)-10-t-butyldimethylsilyloxy-2-formyl-3-heptyloxy-5,9-dimethyl-6,7,8,9-tetrahydro-5,9-methano-5H-benzocycloheptene dissolved in 10 ml of abs. DMF were slowly added dropwise thereto. Then, the cooling bath was removed and the mixture was left to react at room temperature for 2 hours. It was then poured into ice/NH4Cl solution, extracted with diethyl ether, washed with NaCl solution, dried over Na2SO4 and concentrated. Flash chromatography on SiO2 (hexane/ethyl acetate 98/2) gave 2.32 g of ethyl (E)-4-[2-[(5RS,9SR,10RS)-10-t-butyldimethylsilyloxy-3-heptyloxy-5,9-dimethyl-6,7,8,9-tetrahydro-5,9-methano-5H-benzocyclohepten-2-yl]vinyl]benzoate as a yellowish oil. The mixture was cooled to −10° C. Then, the cooling bath was removed the mixture was left to react at room temperature for 2 hours extracted with diethyl ether washed with NaCl solution dried over Na2SO4 concentrated