ethyl 2-[3-(chloromethyl)phenoxy]acetate

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

Procedure: Diethyl acetamidomalonate (2.60 g) and ethyl 3-(chloromethyl)phenoxyacetate (Robertson, J. Chem. Soc. 1933), 492; U.S. Pat. No. 3,933,895) (2.39 g) were dissolved in ethanolic ethoxide (prepared from sodium (230 g) and absolute ethanol (10 ml) and the mixture refluxed for 19 hours. The cooled solution was poured into ice-water, the product was extracted into ether, and the dried extract evaporated. The residual gum was crystallised from ether/hexane to give diethyl acetamido-(3-ethoxycarbonylmethoxyphenyl)malonate as white prisms, m.p. 98.5°-101.5°. This derivative (1.90 g) was refluxed with 10% aqueous hydrochloric acid (25 ml) for 31/2 hours and the cooled solution was evaporated to dryness in vacuo. The residual white solid was dissolved in the minimum quantity of absolute ethanol and added dropwise to a stirred, cooled (-10° C.) mixture of absolute ethanol (15 ml) and thionyl chloride (1.64 g). The resulting solution was set aside at room temperature for 18 hours, refluxed for 1 hour, cooled, and poured into ice-water, adjusting the pH to 9-10 with aqueous sodium hydroxide. The mixture was extracted with ether, and the dried extract was concentrated, giving ethyl 2-amino-3-(3-ethoxycarbonylmethoxyphenyl)propionate as a colourless oil, which was used without further purification in Examples 20 and 21. the mixture refluxed for 19 hours the product was extracted into ether the dried extract evaporated The residual gum was crystallised from ether/hexane

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

Procedure: Diethyl acetamidomalonate (2.60 g) and ethyl 3-(chloromethyl)phenoxyacetate (Robertson, J. Chem. Soc. (1933), 492; U.S. Pat. No. 3,933,895) (2.39 g) were dissolved in ethanolic ethoxide (prepared from sodium (230 mg) and absolute ethanol (10 ml)) and the mixture refluxed for 19 hours. The cooled solution was poured into ice-water, the product was extracted into ether, and the dried extract evaporated. The residual gum was crystallised from ether/hexane to give diethyl acetamido-(3-ethoxycarbonylmethoxyphenyl)malonate as white prisms, m.p. 98.5°-101.5°. This derivative (1.90 g) was refluxed with 10% aqueous hydrochloric acid (25 ml) for 31/2 hours and the cooled solution was evaporated to dryness in vacuo. The residual white solid was dissolved in the minimum quantity of absolute ethanol and added dropwise to a stirred, cooled (-10° C.) mixture of absolute ethanol (15 ml) and thionyl chloride (1.64 g). The resulting solution was set aside at room temperature for 18 hours, refluxed for 1 hour, cooled, and poured into ice-water, adjusting the pH to 9-10 with aqueous sodium hydroxide. The mixture was extracted with ether, and the dried extract was concentrated, giving ethyl 2-amino-3-(3-ethoxycarbonylmethoxyphenyl)propionate as a colourless oil, which was used without further purification in Examples 20 and 21. the mixture refluxed for 19 hours the product was extracted into ether the dried extract evaporated The residual gum was crystallised from ether/hexane

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

Procedure: Diethyl acetamidomalonate (2.60 g) and ethyl 3-(chloromethyl)phenoxyacetate (Robertson, J. Chem. Soc. 1933), 492; U.S. Pat. No. 3,933,895) (2.39 g) were dissolved in ethanolic ethoxide (prepared from sodium (230 mg) and absolute ethanol (10 ml) and the mixture refluxed for 19 hours. The cooled solution was poured into ice-water, the product was extracted into ether, and the dried extract evaporated. The residual gum was crystallised from ether/hexane to give diethyl acetamido-(3-ethoxycarbonylmethoxyphenyl)malonate as white prisms, m.p. 98.5°-101.5°. This derivative (1.90 g) was refluxed with 10% aqueous hydrochloric acid (25 ml) for 31/2 hours and the cooled solution was evaporated to dryness in vacuo. The residual white solid was dissolved in the minimum quantity of absolute ethanol and added dropwise to a stirred, cooled (-10° C.) mixture of absolute ethanol 815 ml) and thionyl chloride (1.64 g). The resulting solution was set aside at room temperature for 18 hours, refluxed for 1 hour, cooled, and poured into ice-water, adjusting the pH to 9-10 with aqueous sodium hydroxide. The mixture was extracted with ether, and the dried extract was concentrated, giving ehtyl 2-amino-3-(3-ethoxycarbonylmethoxyphenyl)propionate as a colourless oil, which was used without further purification in Examples 20 and 21. the mixture refluxed for 19 hours the product was extracted into ether the dried extract evaporated The residual gum was crystallised from ether/hexane

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

Procedure: Diethyl acetamidomalonate (2.60 g) and ethyl 3-(chloromethyl)phenoxyacetate (Robertson, J. Chem. Soc. 1933), 492; U.S. Pat. No. 3,933,895) (2.39 g) were dissolved in ethanolic ethoxide (prepared from sodium (230 g) and absolute ethanol (10 ml) and the mixture refluxed for 19 hours. The cooled solution was poured into ice-water, the product was extracted into ether, and the dried extract evaporated. The residual gum was crystallised from ether/hexane to give diethyl acetamido-(3-ethoxycarbonylmethoxyphenyl)malonate as white prisms, m.p. 98.5°-101.5°. This derivative (1.90 g) was refluxed with 10% aqueous hydrochloric acid (25 ml) for 31/2 hours and the cooled solution was evaporated to dryness in vacuo. The residual white solid was dissolved in the minimum quantity of absolute ethanol and added dropwise to a stirred, cooled (-10° C.) mixture of absolute ethanol (15 ml) and thionyl chloride (1.64 g). The resulting solution was set aside at room temperature for 18 hours, refluxed for 1 hour, cooled, and poured into ice-water, adjusting the pH to 9-10 with aqueous sodium hydroxide. The mixture was extracted with ether, and the dried extract was concentrated, giving ethyl 2-amino-3-(3-ethoxycarbonylmethoxyphenyl)propionate as a colourless oil, which was used without further purification in Examples 20 and 21. the mixture refluxed for 19 hours the product was extracted into ether the dried extract evaporated The residual gum was crystallised from ether/hexane