methyl 3-(4-fluoroanilino)-3-oxopropanoate

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

Procedure: A mixture of methyl 2-[N-(4-fluorophenyl)carbamoyl]acetate (10 g), carbon disulfide (3.2 ml) and acetone (200 ml) was cooled to 5°-10° C., to which 50% aqueous sodium hydroxide (4.2 ml) was added dropwise. The mixture was stirred at same temperature for 2 hrs, then dibromomethane (4 ml) was added dropwise and the reaction mixture was stirred at room temperature for 1 hr and refluxed for 2 hrs. The solid was removed by filtration and the filtrate was poured onto ice-water. The solid formed was filtered, and dissolved in methylene chloride. The solution was washed with 10% aqueous sodium hydroxide solution and water, then dried. The solvent was evaporated and the residue was purified with ethyl acetate and ethyl ether to give the titled compound as a white solid. (8.5 g, 60%). was added dropwise the reaction mixture was stirred at room temperature for 1 hr refluxed for 2 hrs The solid was removed by filtration the filtrate was poured onto ice-water The solid formed was filtered dissolved in methylene chloride The solution was washed with 10% aqueous sodium hydroxide solution and water dried The solvent was evaporated the residue was purified with ethyl acetate and ethyl ether

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

Procedure: A mixture of methyl 2-[N-(4-fluorophenyl)carbamoyl]acetate (10 g), carbon disulfide (3.2 ml) and acetone (200 ml) was cooled to 5°-10° C., to which 50% aqueous sodium hydroxide (4.2 ml) was added dropwise. The mixture was stirred at same temperature for 2 hrs, then dibromomethane (4 ml) was added dropwise and the reaction mixture was stirred at room temperature for 1 hr and refluxed for 2 hrs. The solid was removed by filtration and the filtrate was poured onto ice-water. The solid formed was filtered, and dissolved in methylene chloride. The solution was washed with 10% aqueous sodium hydroxide solution and water, then dried. The solvent was evaporated and the residue was purified with ethyl acetate and ethyl ether to give the titled compound as a white solid. (8.5 g, 60%). was added dropwise the reaction mixture was stirred at room temperature for 1 hr refluxed for 2 hrs The solid was removed by filtration the filtrate was poured onto ice-water The solid formed was filtered dissolved in methylene chloride The solution was washed with 10% aqueous sodium hydroxide solution and water dried The solvent was evaporated the residue was purified with ethyl acetate and ethyl ether

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

Procedure: To a solution of methyl 3-(4-fluorophenylamino)-3-oxopropanoate(10.1 g, 48 mmol) in EtOH (100 mL) is added trans-4-methoxy-3-buten-2-one (5.7 g, 57 mmol) and CH3ONa (3.1 g, 57 mmol). The mixture is heated at reflux overnight and then concentrated. The residue is purified by silica gel column chromatography eluting with PE:EtOAC (from 5:1 to 2:1) to give the product (2.1 g, 16% yield). MS (m/z): 276.1 (M+H). The mixture is heated at reflux overnight concentrated The residue is purified by silica gel column chromatography eluting with PE

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

Procedure: To a solution of methyl 3-(4-fluorophenylamino)-3-oxopropanoate(10.1 g, 48 mmol) in EtOH (100 mL) is added trans-4-methoxy-3-buten-2-one (5.7 g, 57 mmol) and CH3ONa (3.1 g, 57 mmol). The mixture is heated at reflux overnight and then concentrated. The residue is purified by silica gel column chromatography eluting with PE:EtOAC (from 5:1 to 2:1) to give the product (2.1 g, 16% yield). MS (m/z): 276.1 (M+H). The mixture is heated at reflux overnight concentrated The residue is purified by silica gel column chromatography eluting with PE

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

Procedure: A mixture of methyl 2-[N-(4-fluorophenyl)carbamoyl]acetate (10 g), carbon disulfide (3.2 ml) and acetone (200 ml) was cooled to 5°-10° C., to which 50% aqueous sodium hydroxide (4.2 ml) was added dropwise. The mixture was stirred at same temperature for 2 hrs, then dibromomethane (4 ml) was added dropwise and the reaction mixture was stirred at room temperature for 1 hr and refluxed for 2 hrs. The solid was removed by filtration and the filtrate was poured onto ice-water. The solid formed was filtered, and dissolved in methylene chloride. The solution was washed with 10% aqueous sodium hydroxide solution and water, then dried. The solvent was evaporated and the residue was purified with ethyl acetate and ethyl ether to give the titled compound as a white solid. (8.5 g, 60%). was added dropwise the reaction mixture was stirred at room temperature for 1 hr refluxed for 2 hrs The solid was removed by filtration the filtrate was poured onto ice-water The solid formed was filtered dissolved in methylene chloride The solution was washed with 10% aqueous sodium hydroxide solution and water dried The solvent was evaporated the residue was purified with ethyl acetate and ethyl ether