methyl 2-(3-chloroanilino)acetate

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

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

Procedure: A mixture of sodium bicarbonate (66 g), 3-chloroaniline (50 g) and methyl chloroacetate (51.5 ml) were stirred under nitrogen at 80°-100° for 6 h. Heating at 90° was continued overnight, and the mixture was then cooled and poured into ether (400 ml). The resultant suspension was stirred, chilled to 0°, the precipitated solid was filtered off and the filtrate was retained. The solid was dissolved in ethyl acetate (400 ml) and washed with water (2×200 ml), followed by dilute hydrochloric acid (200 ml). The organic phase was dried and concentrated in vacuo to give the title compound (16.4 g) as a solid, m.p. 75°-76°. The previously obtained filtrate was washed with dilute hydrochloric acid (200 ml), and the organic phase was separated, dried and concentrated in vacuo to give an oily solid. This was triturated with ether:hexane (1:1; 300 ml) and filtered off to give a further batch of the title compound (20 g). Heating at 90° was continued overnight the mixture was then cooled chilled to 0° the precipitated solid was filtered off The solid was dissolved in ethyl acetate (400 ml) washed with water (2×200 ml) The organic phase was dried concentrated in vacuo

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

Procedure: To a solution of Boc-glycine and triethylamine (1.0 equiv.) in dichloromethane at 0° C. is added oxalylchloride (1.0 equiv). After one hour, a solution of the product from Step F (1 equiv.) in dichloromethane is added to the first solution, followed by triethylamine (1 equiv.). The solution is allowed to warm to room temperature. After complete reaction, the solution is poured into EtOAc and washed with sat. NH4Cl soln., sat. NaHCO3 soln., and brine. The solution is dried (Na2SO4), filtered, and concentrated in vacuo. The resulting material is purified by silica gel chromatography to provide the titled compound. After complete reaction washed with sat. NH4Cl soln The solution is dried (Na2SO4) filtered concentrated in vacuo The resulting material is purified by silica gel chromatography

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

Procedure: To a solution of Boc-glycine and triethylamine (1.0 equiv.) in dichloromethane at 0° C. is added oxalylchloride (1.0 equiv). After one hour, a solution of the product from Step F (1 equiv.) in dichloromethane is added to the first solution, followed by triethylamine (1 equiv.). The solution is allowed to warm to room temperature. After complete reaction, the solution is poured into EtOAc and washed with sat. NH4Cl soln., sat. NaHCO3 soln., and brine. The solution is dried (Na2SO4), filtered, and concentrated in vacuo. The resulting material is purified by silica gel chromatography to provide the titled compound. After complete reaction washed with sat. NH4Cl soln The solution is dried (Na2SO4) filtered concentrated in vacuo The resulting material is purified by silica gel chromatography

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-chloroaniline and potassium carbonate (3 equiv.) in DMF is added methylbromoacetate (1.1 equiv.), and the reaction is stirred at 60° C. After complete reaction, the solution is poured into EtOAc and washed with water, sat. aq. NaHCO3 soln., and brine. The solution is dried (Na2SO4), filtered, and concentrated in vacuo. The resulting material is purified by silica gel chromatography to provide the titled compound. After complete reaction washed with water, sat. aq. NaHCO3 soln The solution is dried (Na2SO4) filtered concentrated in vacuo The resulting material is purified by silica gel chromatography

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

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (3-Chloro-phenylamino)-acetic acid methyl ester (4 g, 20.0 mmol) and sodium hydroxide (4.00 g, 100 mmol) were combined in ethanol (60.0 mL) and water (10 mL) to give a light yellow solution which was heated at 60° C. for 4 hours. The reaction mixture was cooled to ambient temperature, diluted with ethyl acetate and washed with 1M aqueous hydrochloric acid. The organic layer was separated, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give (3-chloro-phenylamino)-acetic acid as a brown solid (3.20 g, 86%). The reaction mixture was cooled to ambient temperature washed with 1M aqueous hydrochloric acid The organic layer was separated dried over anhydrous sodium sulfate filtered concentrated in vacuo

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl bromoacetate (8.3 g, 54.3 mmol), 3-chloroaniline (8.31 g, 65.1 mmol) and diisopropylethylamine (7.01 g, 54.3 mmol) were dissolved in N,N-dimethylformamide (20 mL) to give a light yellow solution and the reaction mixture heated at 60° C. overnight. The reaction mixture was cooled to ambient temperature, diluted with ethyl acetate and washed with brine. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to give (3-chloro-phenylamino)-acetic acid methyl ester as a solid which was washed with hexanes, filtered and dried (10.2 g, 96%). to give a light yellow solution The reaction mixture was cooled to ambient temperature washed with brine The organic layer was dried over sodium sulfate filtered concentrated in vacuo

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

Procedure: A mixture of sodium bicarbonate (66 g), 3-chloroaniline (50 g) and methyl chloroacetate (51.5 ml) were stirred under nitrogen at 80°-100° for 6 h. Heating at 90° was continued overnight, and the mixture was then cooled and poured into ether (400 ml). The resultant suspension was stirred, chilled to 0°, the precipitated solid was filtered off and the filtrate was retained. The solid was dissolved in ethyl acetate (400 ml) and washed with water (2×200 ml), followed by dilute hydrochloric acid (200 ml). The organic phase was dried and concentrated in vacuo to give the title compound (16.4 g) as a solid, m.p. 75°-76°. The previously obtained filtrate was washed with dilute hydrochloric acid (200 ml), and the organic phase was separated, dried and concentrated in vacuo to give an oily solid. This was triturated with ether:hexane (1:1; 300 ml) and filtered off to give a further batch of the title compound (20 g). Heating at 90° was continued overnight the mixture was then cooled chilled to 0° the precipitated solid was filtered off The solid was dissolved in ethyl acetate (400 ml) washed with water (2×200 ml) The organic phase was dried concentrated in vacuo

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

Procedure: To a solution of Boc-glycine and triethylamine (1.0 equiv.) in dichloromethane at 0° C. is added oxalylchloride (1.0 equiv). After one hour, a solution of the product from Step F (1 equiv.) in dichloromethane is added to the first solution, followed by triethylamine (1 equiv.). The solution is allowed to warm to room temperature. After complete reaction, the solution is poured into EtOAc and washed with sat. NH4Cl soln., sat. NaHCO3 soln., and brine. The solution is dried (Na2SO4), filtered, and concentrated in vacuo. The resulting material is purified by silica gel chromatography to provide the titled compound. After complete reaction washed with sat. NH4Cl soln The solution is dried (Na2SO4) filtered concentrated in vacuo The resulting material is purified by silica gel chromatography

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-chloroaniline and potassium carbonate (3 equiv.) in DMF is added methylbromoacetate (1.1 equiv.), and the reaction is stirred at 60° C. After complete reaction, the solution is poured into EtOAc and washed with water, sat. aq. NaHCO3 soln., and brine. The solution is dried (Na2SO4), filtered, and concentrated in vacuo. The resulting material is purified by silica gel chromatography to provide the titled compound. After complete reaction washed with water, sat. aq. NaHCO3 soln The solution is dried (Na2SO4) filtered concentrated in vacuo The resulting material is purified by silica gel chromatography