ethyl 2-diethoxyphosphorylpropanoate

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:0.00; pressure:0.00; stir:

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

Procedure: To a suspension of potassium tert-butoxide (183.1 g, 1.63 mol) in toluene (1400 ml) under an atmosphere of nitrogen was slowly added triethyl 2-phosponopropionate (361.1 g, 1.52 mol) with ice cooling at such a rate that the internal temperature was maintained at approximately 20° C. The resultant yellow solution was stirred at room temperature for 3 h after which time it was cooled in an ice bath. To this cooled solution was added a solution of 3-bromoacetophenone (274.2 g, 1.38 mol) in toluene (400 ml) at such a rate that the internal temperature did not rise above 20 ° C. The resultant red-brown solution was then stirred at room temperature for 18 h. After this time, more potassium tert-butoxide (38.7 g, 0.34 mol) was added, and the resultant mixture was stirred at room temperature for an additional 20 h. The reaction was quenched by the cautious addition of water (2000 ml), and the layers were separated. The organic layer was washed with water (4×2000 ml), and was then concentrated in vacuo to give the crude product as a brown oil (344 g) which was distilled under reduced pressure to give the impure title compound (2:3 mixture of geometric isomers) as a colourless liquid (212 g) which was contaminated with small amounts of triethyl 2-phosphonopropionate and 3-bromoacetophenone. In the present synthetic route the impure title compound was taken forward into the next step without any further purification. However, purification, for example using flash chromatography eluting with 5% ethyl acetate in hexane, affords the analytically pure title compound as a clear colourless oil. In the present synthetic route the impure title compound was taken forward into the next step without any further purification However, purification eluting with 5% ethyl acetate in hexane

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

Procedure: To a suspension of potassium tert-butoxide (183.1 g, 1.63 mol) in toluene (1400 ml) under an atmosphere of nitrogen was slowly added triethyl 2-phosponopropionate (361.1 g, 1.52 mol) with ice cooling at such a rate that the internal temperature was maintained at approximately 20° C. The resultant yellow solution was stirred at room temperature for 3 h after which time it was cooled in an ice bath. To this cooled solution was added a solution of 3-bromoacetophenone (274.2 g, 1.38 mol) in toluene (400 ml) at such a rate that the internal temperature did not rise above 20 ° C. The resultant red-brown solution was then stirred at room temperature for 18 h. After this time, more potassium tert-butoxide (38.7 g, 0.34 mol) was added, and the resultant mixture was stirred at room temperature for an additional 20 h. The reaction was quenched by the cautious addition of water (2000 ml), and the layers were separated. The organic layer was washed with water (4×2000 ml), and was then concentrated in vacuo to give the crude product as a brown oil (344 g) which was distilled under reduced pressure to give the impure title compound (2:3 mixture of geometric isomers) as a colourless liquid (212 g) which was contaminated with small amounts of triethyl 2-phosphonopropionate and 3-bromoacetophenone. In the present synthetic route the impure title compound was taken forward into the next step without any further purification. However, purification, for example using flash chromatography eluting with 5% ethyl acetate in hexane, affords the analytically pure title compound as a clear colourless oil. was cooled in an ice bath did not rise above 20 ° C The resultant red-brown solution was then stirred at room temperature for 18 h The reaction was quenched by the cautious addition of water (2000 ml) the layers were separated The organic layer was washed with water (4×2000 ml) was then concentrated in vacuo to give the crude product as a brown oil (344 g) which was distilled under reduced pressure

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

Procedure: A solution of 1.8 g (7.7 mmol) of triethyl 2-phosphonopropionate in 25 mL of tetrahydrofuran is added to a suspension of 310 mg (7.7 mmol) of 60% sodium hydride in oil, precooled to 0° C. After stirring at 0° C. for 15 minutes, a solution of 1.5 g (5.2 mmol) of 4-iodo-3-propoxybenzaldehyde in 10 mL of tetrahydrofuran is added. The reaction medium is stirred at room temperature for 12 hours. Saturated ammonium chloride solution is added and the reaction medium is extracted with ethyl acetate. The organic phase is dried over magnesium sulfate, filtered and evaporated. The residue obtained is purified by chromatography on a column of silica eluted with a 7/3 heptane/ethyl acetate mixture. 1.6 g (84%) of ethyl (E)-3-(4-iodo-3-propoxyphenyl)-2-methylacrylate are obtained. precooled to 0° C The reaction medium is stirred at room temperature for 12 hours the reaction medium is extracted with ethyl acetate The organic phase is dried over magnesium sulfate filtered evaporated The residue obtained is purified by chromatography on a column of silica eluted with a 7/3 heptane/ethyl acetate mixture

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

Procedure: To a solution of 5.1 g of sodium hydride in oil (prewashed by decantation with hexane.) in 60 ml of dry tetrahydrofuran was added dropwise 30 g of triethyl 2-phosphonopropionate over a period of 30 minutes under dry argon atmosphere at room temperature. After the mixture was stirred for further 1 hour, a solution of 11.8 g of 2-thiophenealdehyde in 30 ml of tetrahydrofuran was added dropwise. The mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into water, and extracted with ethyl acetate. The extract was washed successively with water and saturated saline, dried over anhydrous magnesium sulfate. Drying agent was removed by filtration, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel to give 11.0 g of ethyl 2-methyl-3-(2-thienyl)acrylate as a yellow oil. Next, 150 ml of ethanol and 60 ml of aqueous 2N sodium hydroxide were added to the oil, and the mixture was refluxed for 1 hour. After cooling, ethanol was removed under reduced pressure, and the residue was acidified with dilute hydrochloric acid. Crystalline precipitate was collected by filtration to give 8.2 g of 2-methyl-3-(2-thienyl)acrylic acid as a white powder. The mixture was stirred at room temperature for 2 hours extracted with ethyl acetate The extract was washed successively with water and saturated saline dried over anhydrous magnesium sulfate Drying agent was removed by filtration the solvent was removed under reduced pressure The residue was purified by column chromatography on silica gel

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

Procedure: To a solution of triethyl 2-phosphonopropionate (47 g, 0.19 mol) in THF (200 mL) was added solid magnesium bromide etherate (59 g, 0.23 mol) under nitrogen. Triethylamine (26.5 mL, 0.19 mol) was added after 5 min. The mixture was stirred for 10 min and 4-(methylthio)benzaldehyde (27.1 mL, 0.19 mol) was added. After 15 h at room temperature the mixture was diluted with water (400 mL) and hexane (400 mL). The two layers were separated. The organic layer was washed with water (400 mL), dried over 4 Å molecular sieves, filtered, and concentrated to give 42.5 g (95%) of ester 6a as a light yellow oil: IR (neat) 2980, 1705, and 1240 cm-1 ; 1H NMR (CDCl3, 300 MHz) δ 7.63 (1 H), 7.33 (2 H), 7.25 (2 H), 4.26 (2 H), 2.50 (3 H), 2.12 (3 H), and 1.34 (3 H); 13C NMR (CDCl3, 75.5 MHz) δ 168.71, 139.37, 138.08, 132.55, 130.19, 127.98, 125.89, 60.87, 15.38, 14.37 and 14.17. The two layers were separated The organic layer was washed with water (400 mL) dried over 4 Å molecular sieves filtered concentrated

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

Procedure: 5H-Dibenzo[a,d]cyclohepten-5-one is reacted with triethyl 2-phosphonopropionate in a manner similar to Example 1, to yield the title compound, m.p. 235°-236° C. (uncorr.)

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