methyl 2-[(2-chloroacetyl)amino]benzoate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of methyl 2-aminobenzoate (906 mg, 6.0 mmol) and NaHCO3 (554.4 mg, 6.6 mmol) in THF (12 mL) and water (12 mL) at 0° C. was added 2-chloroacetyl chloride (806 mg, 7.2 mmol) dropwise. After 2 hours, the mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to afford the crude product. The residue was purified by flash chromatography to give methyl 2-(2-chloroacetamido)benzoate (1.31 g, 96%). LC-MS (ES-API); rt 8.65 min; m/z calculated for C10H10ClNO3 [M+Na]+ 250.0, found 250.0. extracted with ethyl acetate The organic layer was washed with brine dried over sodium sulfate concentrated under reduced pressure to afford the crude product The residue was purified by flash chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 10.06 Grams of methyl o-(α-chloroacetylamino)benzoate, 15.2 g of N-(3,4-dimethoxybenzoyl)piperzine.monohydrochloride and 16 g of triethylamine were suspended in 55 ml of acetonitrile, and the mixture was reacted at 49°-50° C. for 4 hours. After completion of the reaction, the reaction mixture was ice-cooled, and the crystals formed were collected by filtration. Recrystallized from ethanol to obtain 14.68 g of o-methoxycarbonyl-α-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]acetanilide in the form of colorless needle-like crystals. Melting point: 167.5°-169.0° C. the mixture was reacted at 49°-50° C. for 4 hours After completion of the reaction cooled the crystals formed were collected by filtration Recrystallized from ethanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4.3 Grams of piperazine was added to 50 ml of ethanol, to this solution was added 2.3 g of methyl o-(α-chloroacetylamino)benzoate at a temperature of 40°-50° C. with stirring. The reaction mixture was stirred at the same temperature for 3 hours, then the reaction mixture was concentrated, to the obtained residue was added 20 ml of water, then saturated with sodium chloride, and extracted with chloroform. The chloroform layer was washed with a 10%-sodium hydroxide solution, then washed with a small amount of water and dried. After removal of the solvent by distillation, the residue obtained was purified by a silica gel column chromatography, and recrystallized from ether to obtain 2 g of o-methoxycarbonyl-α-(1-piperazinyl)-acetanilide in the form of colorless needle-like crystals. Melting point: 94°-96° C. The reaction mixture was stirred at the same temperature for 3 hours the reaction mixture was concentrated, to the obtained residue was added 20 ml of water saturated with sodium chloride, and extracted with chloroform The chloroform layer was washed with a 10%-sodium hydroxide solution washed with a small amount of water dried After removal of the solvent by distillation the residue obtained was purified by a silica gel column chromatography recrystallized from ether

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 38 Grams of methyl anthranilate and 35 g of potassium carbonate were dissolved in 300 ml of a mixture of acetone-water (2:1), then to this solution was added dropwise 30 g of chloroacetyl chloride under an ice-cooled condition with stirring. After completion of the addition, the reaction was carried out at a room temperature for 2 hours, then 200 ml of water was added to the reaction mixture, and the mixture obtained was ice-cooled, and the crystals precipitated were collected by filtration. The crystals collected were washed with water and ethanol, and recrystallized from methanol to obtain 48.6 g of methyl o-(α-chloroacetylamino)benzoate in the form of colorless needle-like crystals. Melting point: 97°-99° C. cooled condition After completion of the addition the mixture obtained cooled the crystals precipitated were collected by filtration The crystals collected were washed with water and ethanol recrystallized from methanol