ethyl 5-amino-2-chlorobenzoate

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

Procedure: To the mixture of ethyl 5-amino-2-chlorobenzoate, cyclopropanecarboxaldehyde (458 μl) and acetic acid (1.43 ml) dissolved in methanol (20 ml), α-picoline borane (804 mg) was added at ice cool temperature, and was stirred under nitrogen atmosphere overnight at room temperature. After the reaction mixture was concentrated under reduced pressure, sodium hydrogencarbonate aqueous solution was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography, and ethyl 2-chloro-5-(cyclopropylmethylamino)benzoate (881 mg) and ethyl 5-[bis(cyclopropylmethyl)amino]-2-chlorobenzoate (423 mg) were obtained. cool temperature After the reaction mixture was concentrated under reduced pressure, sodium hydrogencarbonate aqueous solution was added to the residue the mixture was extracted with ethyl acetate The organic layer was washed with brine dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by silica gel chromatography, and ethyl 2-chloro-5-(cyclopropylmethylamino)benzoate (881 mg)

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Thionyl chloride (4.0 g, 0.034 mole) was added to a stirred mixture of 2-ethyl-5,6-dihydro-1,4-oxathiin-3-carboxylic acid (5.9 g, 0.034 mole) and methylene chloride (100 ml). The mixture was warmed to about 35° C. for 3 hours, then evaporated under reduced pressure. The residue, crude 2-ethyl-5,6-dihydro-1,4-oxathiin-3-carbonyl chloride, was dissolved in methylene chloride (100 ml), and the ice-chilled solution treated dropwise with a solution of ethyl 5-amino-2-chlorobenzoate (6.8 g, 0.034 mole) and triethylamine (3.7 g, 0.037 mole) in methylene chloride (100 ml). The reaction mixture was stirred overnight at room temperature and then worked up by washing in sequence with water, dilute hydrochloric acid, water, 2% sodium hydroxide and water. Evaporation of the solvent left an oil, which solidified. After recrystallization from ethanol (30 ml) the product (7.0 g, 58% yield) melted at 86°-88° C. evaporated under reduced pressure The residue, crude 2-ethyl-5,6-dihydro-1,4-oxathiin-3-carbonyl chloride, was dissolved in methylene chloride (100 ml) the ice-chilled solution by washing in sequence with water, dilute hydrochloric acid, water, 2% sodium hydroxide and water Evaporation of the solvent left an oil, which

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

Procedure: To the mixture of ethyl 5-amino-2-chlorobenzoate, cyclopropanecarboxaldehyde (458 μl) and acetic acid (1.43 ml) dissolved in methanol (20 ml), α-picoline borane (804 mg) was added at ice cool temperature, and was stirred under nitrogen atmosphere overnight at room temperature. After the reaction mixture was concentrated under reduced pressure, sodium hydrogencarbonate aqueous solution was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography, and ethyl 2-chloro-5-(cyclopropylmethylamino)benzoate (881 mg) and ethyl 5-[bis(cyclopropylmethyl)amino]-2-chlorobenzoate (423 mg) were obtained. cool temperature After the reaction mixture was concentrated under reduced pressure, sodium hydrogencarbonate aqueous solution was added to the residue the mixture was extracted with ethyl acetate The organic layer was washed with brine dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by silica gel chromatography, and ethyl 2-chloro-5-(cyclopropylmethylamino)benzoate (881 mg)

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

Procedure: To the mixture of ethyl 5-amino-2-chlorobenzoate, cyclopropanecarboxaldehyde (458 μl) and acetic acid (1.43 ml) dissolved in methanol (20 ml), α-picoline borane (804 mg) was added at ice cool temperature, and was stirred under nitrogen atmosphere overnight at room temperature. After the reaction mixture was concentrated under reduced pressure, sodium hydrogencarbonate aqueous solution was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography, and ethyl 2-chloro-5-(cyclopropylmethylamino)benzoate (881 mg) and ethyl 5-[bis(cyclopropylmethyl)amino]-2-chlorobenzoate (423 mg) were obtained. cool temperature After the reaction mixture was concentrated under reduced pressure, sodium hydrogencarbonate aqueous solution was added to the residue the mixture was extracted with ethyl acetate The organic layer was washed with brine dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by silica gel chromatography, and ethyl 2-chloro-5-(cyclopropylmethylamino)benzoate (881 mg)

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Thionyl chloride (4.0 g, 0.034 mole) was added to a stirred mixture of 2-ethyl-5,6-dihydro-1,4-oxathiin-3-carboxylic acid (5.9 g, 0.034 mole) and methylene chloride (100 ml). The mixture was warmed to about 35° C. for 3 hours, then evaporated under reduced pressure. The residue, crude 2-ethyl-5,6-dihydro-1,4-oxathiin-3-carbonyl chloride, was dissolved in methylene chloride (100 ml), and the ice-chilled solution treated dropwise with a solution of ethyl 5-amino-2-chlorobenzoate (6.8 g, 0.034 mole) and triethylamine (3.7 g, 0.037 mole) in methylene chloride (100 ml). The reaction mixture was stirred overnight at room temperature and then worked up by washing in sequence with water, dilute hydrochloric acid, water, 2% sodium hydroxide and water. Evaporation of the solvent left an oil, which solidified. After recrystallization from ethanol (30 ml) the product (7.0 g, 58% yield) melted at 86°-88° C. evaporated under reduced pressure The residue, crude 2-ethyl-5,6-dihydro-1,4-oxathiin-3-carbonyl chloride, was dissolved in methylene chloride (100 ml) the ice-chilled solution by washing in sequence with water, dilute hydrochloric acid, water, 2% sodium hydroxide and water Evaporation of the solvent left an oil, which

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Thionyl chloride (4.0 g, 0.034 mole) was added to a stirred mixture of 2-ethyl-5,6-dihydro-1,4-oxathiin-3-carboxylic acid (5.9 g, 0.034 mole) and methylene chloride (100 ml). The mixture was warmed to about 35° C. for 3 hours, then evaporated under reduced pressure. The residue, crude 2-ethyl-5,6-dihydro-1,4-oxathiin-3-carbonyl chloride, was dissolved in methylene chloride (100 ml), and the ice-chilled solution treated dropwise with a solution of ethyl 5-amino-2-chlorobenzoate (6.8 g, 0.034 mole) and triethylamine (3.7 g, 0.037 mole) in methylene chloride (100 ml). The reaction mixture was stirred overnight at room temperature and then worked up by washing in sequence with water, dilute hydrochloric acid, water, 2% sodium hydroxide and water. Evaporation of the solvent left an oil, which solidified. After recrystallization from ethanol (30 ml) the product (7.0 g, 58% yield) melted at 86°-88° C. evaporated under reduced pressure The residue, crude 2-ethyl-5,6-dihydro-1,4-oxathiin-3-carbonyl chloride, was dissolved in methylene chloride (100 ml) the ice-chilled solution by washing in sequence with water, dilute hydrochloric acid, water, 2% sodium hydroxide and water Evaporation of the solvent left an oil, which

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Thionyl chloride (4.0 g, 0.034 mole) was added to a stirred mixture of 2-ethyl-5,6-dihydro-1,4-oxathiin-3-carboxylic acid (5.9 g, 0.034 mole) and methylene chloride (100 ml). The mixture was warmed to about 35° C. for 3 hours, then evaporated under reduced pressure. The residue, crude 2-ethyl-5,6-dihydro-1,4-oxathiin-3-carbonyl chloride, was dissolved in methylene chloride (100 ml), and the ice-chilled solution treated dropwise with a solution of ethyl 5-amino-2-chlorobenzoate (6.8 g, 0.034 mole) and triethylamine (3.7 g, 0.037 mole) in methylene chloride (100 ml). The reaction mixture was stirred overnight at room temperature and then worked up by washing in sequence with water, dilute hydrochloric acid, water, 2% sodium hydroxide and water. Evaporation of the solvent left an oil, which solidified. After recrystallization from ethanol (30 ml) the product (7.0 g, 58% yield) melted at 86°-88° C. evaporated under reduced pressure The residue, crude 2-ethyl-5,6-dihydro-1,4-oxathiin-3-carbonyl chloride, was dissolved in methylene chloride (100 ml) the ice-chilled solution by washing in sequence with water, dilute hydrochloric acid, water, 2% sodium hydroxide and water Evaporation of the solvent left an oil, which

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

Procedure: To the mixture of ethyl 5-amino-2-chlorobenzoate, cyclopropanecarboxaldehyde (458 μl) and acetic acid (1.43 ml) dissolved in methanol (20 ml), α-picoline borane (804 mg) was added at ice cool temperature, and was stirred under nitrogen atmosphere overnight at room temperature. After the reaction mixture was concentrated under reduced pressure, sodium hydrogencarbonate aqueous solution was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography, and ethyl 2-chloro-5-(cyclopropylmethylamino)benzoate (881 mg) and ethyl 5-[bis(cyclopropylmethyl)amino]-2-chlorobenzoate (423 mg) were obtained. cool temperature After the reaction mixture was concentrated under reduced pressure, sodium hydrogencarbonate aqueous solution was added to the residue the mixture was extracted with ethyl acetate The organic layer was washed with brine dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by silica gel chromatography, and ethyl 2-chloro-5-(cyclopropylmethylamino)benzoate (881 mg)

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Thionyl chloride (4.0 g, 0.034 mole) was added to a stirred mixture of 2-ethyl-5,6-dihydro-1,4-oxathiin-3-carboxylic acid (5.9 g, 0.034 mole) and methylene chloride (100 ml). The mixture was warmed to about 35° C. for 3 hours, then evaporated under reduced pressure. The residue, crude 2-ethyl-5,6-dihydro-1,4-oxathiin-3-carbonyl chloride, was dissolved in methylene chloride (100 ml), and the ice-chilled solution treated dropwise with a solution of ethyl 5-amino-2-chlorobenzoate (6.8 g, 0.034 mole) and triethylamine (3.7 g, 0.037 mole) in methylene chloride (100 ml). The reaction mixture was stirred overnight at room temperature and then worked up by washing in sequence with water, dilute hydrochloric acid, water, 2% sodium hydroxide and water. Evaporation of the solvent left an oil, which solidified. After recrystallization from ethanol (30 ml) the product (7.0 g, 58% yield) melted at 86°-88° C. evaporated under reduced pressure The residue, crude 2-ethyl-5,6-dihydro-1,4-oxathiin-3-carbonyl chloride, was dissolved in methylene chloride (100 ml) the ice-chilled solution by washing in sequence with water, dilute hydrochloric acid, water, 2% sodium hydroxide and water Evaporation of the solvent left an oil, which