ethyl 3-(4-fluorophenyl)-3-oxopropanoate

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:

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

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

Procedure: Under nitrogen atmosphere, 30 mL of. THF was added to 6.09 g (10 mmol, 1.0 equivalent) of (BrZnCH2COOEt.THF)2. Under argon atmosphere, a solution of 1.21 g (10 mmol) of 4-fluorobenzonitrile in 5 mL of THF was added dropwise while stirring at 0˜5° C. The mixture was stirred at 20˜25° C. for 26 hours. 15 mL of 10% hydrochloric acid was added dropwise at 20° C. or lower, and the mixture was stirred at 20˜25° C. for 1 hour, followed by dilution with ethyl acetate. Then, the layers were separated. The organic layer was washed successively with 15 mL of 1N hydrochloric acid, 20 mL of an aqueous saturated sodium chloride solution, 20 mL (×2) of an aqueous saturated sodium bicarbonate solution, and 20 mL of an aqueous saturated sodium chloride solution. After washing, the organic layer was dried with anhydrous magnesium sulfate. Concentration under reduced pressure afforded 1.96 g of the desired product (yield 93%). The mixture was stirred at 20˜25° C. for 26 hours lower, and the mixture was stirred at 20˜25° C. for 1 hour Then, the layers were separated The organic layer was washed successively with 15 mL of 1N hydrochloric acid, 20 mL of an aqueous saturated sodium chloride solution, 20 mL (×2) of an aqueous saturated sodium bicarbonate solution, and 20 mL of an aqueous saturated sodium chloride solution After washing the organic layer was dried with anhydrous magnesium sulfate Concentration under reduced pressure

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

Procedure: Prepared in analogy to Synthesis Communications (1989) 3:217-218. To a solution of triphenylphosphine oxide (3.77 g, 14 mmol) in 1,2-dichloroethane (42 mL) was added trifluoromethanesulfonic anhydride (2.25 mL, 14 mmol) dropwise at 0° C. and the grey suspension was stirred at 0° C. for 15 min. Then a solution of 3-(4-fluoro-phenyl)-3-oxo-propionic acid ethyl ester (2.85 g, 14 mmol) in 1,2-dichloroethane (14 mL) was added followed by a dropwise addition of triethylamine (3.78 mL, 28 mmol) at 0° C. The brown solution was refluxed for 2.5 h. After cooling the mixture was poured onto ice-water and the organic layer separated and washed with brine, dried over sodium sulphate, filtered and evaporated. Purification by chromatography (silica, 0 to 20% ethyl acetate in heptane) afforded the title compound (1.53 g, 59%) as a yellow solid. MS: m/e=193.2 [M+H]+. Prepared in analogy to Synthesis Communications (1989) 3:217-218 The brown solution was refluxed for 2.5 h After cooling the mixture was poured onto ice-water the organic layer separated washed with brine dried over sodium sulphate filtered evaporated Purification by chromatography (silica, 0 to 20% ethyl acetate in heptane)

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

Procedure: A mixture of 3-amino-2-thiophenecarboxylic acid (8 g, 49 mmol), ethyl 4-fluorobenzoylacetate (9.6 g, 49 mmol), and p-toluenesulfonic acid monohydrate (0.2 g, 1 mmol) in toluene (100 mL) is refluxed for about 20 hours in a flask equipped with a Dean-Stark water trap. The mixture is cooled to room temperature. The precipitate is filtered and washed with diethyl ether. The solid is dissolved in diphenyl ether (80 mL) and heated at 240° C. for about 2 hours. The reaction solution is then cooled to room temperature, diethyl ether is added and the precipitate is filtered and washed with diethyl ether to give 5-(4-fluorophenyl)-thieno[3,2-b]pyridin-7-ol (2 g, 17% yield) as brown crystalline needles, m.p. 316-318 ° C. is refluxed for about 20 hours in a flask The precipitate is filtered washed with diethyl ether The solid is dissolved in diphenyl ether (80 mL) heated at 240° C. for about 2 hours The reaction solution is then cooled to room temperature diethyl ether is added the precipitate is filtered washed with diethyl ether

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

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

Procedure: 25 gms of ethyl 4-fluorobenzoylacetate was dissolved in 250 gms of 1:10 P2O5 /methanesulfonic acid and heated at 45° for 4 days. The mixture was cooled, poured into 1200 mls of water and extracted with (3×100 mls) methylene chloride. Evaporation of the solvent and chromatography of the resulting oil (silica gel/ether) provided 12.9 gms of crystalline 2,6-di(4'-fluorophenyl)-3-ethoxycarbonyl-pyr-4-one. mp=113-114. heated at 45° for 4 days The mixture was cooled extracted with (3×100 mls) methylene chloride Evaporation of the solvent and chromatography of the resulting oil (silica gel/ether)