methyl 5-amino-2-(2-methoxy-2-oxoethyl)benzoate

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

Procedure: 5-amino-2-methoxycarbonylmethyl-benzoic acid methyl ester (5 g, 22.4 mmol) was dissolved in hydrochloric acid (50 mL). To the solution was added dropwise aq.NaNO2 (1.7 g, 24.6 mmol) at below 5° C. After addition completed, the color became maroon. Then CuCl (2.4 g, 24.6 mmol) solution was added to the reaction mixture. The reaction mixture was reacted at below 5° C. for 1 hour. The reaction mixture was extracted with dichloromethane. The organic layer was washed with water, dried over anhydrous Na2SO4, concentrated and purified by column chromatography on silica gel (petroleum ether/ethyl acetate=10/1) to give 2.3 g of 5-chloro-2-methoxycarbonylmethyl-benzoic acid methyl ester (18E). To the solution was added dropwise aq at below 5° C After addition The reaction mixture was reacted at below 5° C. for 1 hour The reaction mixture was extracted with dichloromethane The organic layer was washed with water dried over anhydrous Na2SO4 concentrated purified by column chromatography on silica gel (petroleum ether/ethyl acetate=10/1)

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

Procedure: 5-amino-2-methoxycarbonylmethyl-benzoic acid methyl ester (5 g, 22.4 mmol) was dissolved in hydrochloric acid (50 mL). To the solution was added dropwise aq.NaNO2 (1.7 g, 24.6 mmol) at below 5° C. After addition completed, the color became maroon. Then CuCl (2.4 g, 24.6 mmol) solution was added to the reaction mixture. The reaction mixture was reacted at below 5° C. for 1 hour. The reaction mixture was extracted with dichloromethane. The organic layer was washed with water, dried over anhydrous Na2SO4, concentrated and purified by column chromatography on silica gel (petroleum ether/ethyl acetate=10/1) to give 2.3 g of 5-chloro-2-methoxycarbonylmethyl-benzoic acid methyl ester (18E). To the solution was added dropwise aq at below 5° C After addition The reaction mixture was reacted at below 5° C. for 1 hour The reaction mixture was extracted with dichloromethane The organic layer was washed with water dried over anhydrous Na2SO4 concentrated purified by column chromatography on silica gel (petroleum ether/ethyl acetate=10/1)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-methoxycarbonylmethyl-5-nitro-benzoic acid methyl ester (2.2 g, 8.8 mmol) was dissolved in MeOH (30 mL), then heated to 50° C. To the solution was added SnCl2 (5.89 g, 31 mmol) in batches. The reaction mixture was stirred at this temperture for 1 day. TLC monitored the reaction. After the reaction completed, the solvent was evaporated. To the residue was added ethyl acetate and base, adjusted pH to 8˜9, then filtered though celite and washed with ethyl acetate. The organic layer of the filtrate was collected and washed with water, dried over anhydrous Na2SO4 and concentrated to give 1.3 g of 5-amino-2-methoxycarbonylmethyl-benzoic acid methyl ester (18D). the reaction the solvent was evaporated To the residue was added ethyl acetate and base filtered though celite washed with ethyl acetate The organic layer of the filtrate was collected washed with water dried over anhydrous Na2SO4 concentrated

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

Procedure: 5-amino-2-methoxycarbonylmethyl-benzoic acid methyl ester (5 g, 22.4 mmol) was dissolved in hydrochloric acid (50 mL). To the solution was added dropwise aq.NaNO2 (1.7 g, 24.6 mmol) at below 5° C. After addition completed, the color became maroon. Then CuCl (2.4 g, 24.6 mmol) solution was added to the reaction mixture. The reaction mixture was reacted at below 5° C. for 1 hour. The reaction mixture was extracted with dichloromethane. The organic layer was washed with water, dried over anhydrous Na2SO4, concentrated and purified by column chromatography on silica gel (petroleum ether/ethyl acetate=10/1) to give 2.3 g of 5-chloro-2-methoxycarbonylmethyl-benzoic acid methyl ester (18E). To the solution was added dropwise aq at below 5° C After addition The reaction mixture was reacted at below 5° C. for 1 hour The reaction mixture was extracted with dichloromethane The organic layer was washed with water dried over anhydrous Na2SO4 concentrated purified by column chromatography on silica gel (petroleum ether/ethyl acetate=10/1)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-methoxycarbonylmethyl-5-nitro-benzoic acid methyl ester (2.2 g, 8.8 mmol) was dissolved in MeOH (30 mL), then heated to 50° C. To the solution was added SnCl2 (5.89 g, 31 mmol) in batches. The reaction mixture was stirred at this temperture for 1 day. TLC monitored the reaction. After the reaction completed, the solvent was evaporated. To the residue was added ethyl acetate and base, adjusted pH to 8˜9, then filtered though celite and washed with ethyl acetate. The organic layer of the filtrate was collected and washed with water, dried over anhydrous Na2SO4 and concentrated to give 1.3 g of 5-amino-2-methoxycarbonylmethyl-benzoic acid methyl ester (18D). the reaction the solvent was evaporated To the residue was added ethyl acetate and base filtered though celite washed with ethyl acetate The organic layer of the filtrate was collected washed with water dried over anhydrous Na2SO4 concentrated