methyl 2-amino-2-(4-hydroxyphenyl)acetate

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

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

Procedure: In this preparation 1.81 g. of methyl α-amino-α-(4-hydroxyphenyl)acetate is dissolved in 10 ml. of dimethylformamide under nitrogen and 0.24 g. of sodium hydride is then added. The solution is stirred at room temperature under nitrogen until hydrogen evolution ceases and then 0.80 g. of chloromethyl methyl ether is added. The resulting mixture is warmed at 60° C for 1 hour and then cooled and diluted with water. The aqueous mixture is extracted with ether and the ether extract is dried and evaporated to afford methyl α-amino-α-(4-methoxymethoxyphenyl)acetate. In this preparation 1.81 g cooled The aqueous mixture is extracted with ether the ether extract is dried evaporated

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

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

Procedure: To a 0° solution of 2.50 g (11.48 mmol) of amino-(4-hydroxy-phenyl)-acetic acid methyl ester (from Example 178) in 125 mL of dichloromethane was added 10 mL of N,N-diisopropylethylamine followed by 2.97 g (11.48 mmol) of 9-fluorenylmethyl chlorformate and the resulting mixture was stirred at 0° for 2 h and room temperature for 2 h. The reaction mixture was then concentrated and the residue was diluted with ethyl acetate and water. The organics were washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with ethyl acetate/hexanes (1:3) to provide methyl(2R)-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}(4-hydroxyphenyl)ethanoate as a white solid. Electrospray Mass Spec 404.1 (M+H)+. The reaction mixture was then concentrated the residue was diluted with ethyl acetate and water The organics were washed with water dried over magnesium sulfate filtered concentrated in vacuo The residue was chromatographed on silica gel eluting with ethyl acetate/hexanes (1:3)

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

Procedure: To a 0° solution of 2.50 g (11.48 mmol) of amino-(4-hydroxy-phenyl)-acetic acid methyl ester (from Example 178) in 125 mL of dichloromethane was added 10 mL of N,N-diisopropylethylamine followed by 2.97 g (11.48 mmol) of 9-fluorenylmethyl chlorformate and the resulting mixture was stirred at 0° for 2 h and room temperature for 2 h. The reaction mixture was then concentrated and the residue was diluted with ethyl acetate and water. The organics were washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with ethyl acetate/hexanes (1:3) to provide methyl(2R)-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}(4-hydroxyphenyl)ethanoate as a white solid. Electrospray Mass Spec 404.1 (M+H)+. The reaction mixture was then concentrated the residue was diluted with ethyl acetate and water The organics were washed with water dried over magnesium sulfate filtered concentrated in vacuo The residue was chromatographed on silica gel eluting with ethyl acetate/hexanes (1:3)

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

Procedure: To 50 mL of methanol cooled to 0° C. was dropwise added 3.75 mL of thionyl chloride followed by 5.0 g (0.030 mmol) of D-4-hydroxyphenylglycine. The reaction was heated to reflux for 5 h then stirred overnight at room temperature. The resulting mixture was concentrated in vacuo and the residue was diluted with ether. The resulting solid was collected by filtration and dried in vacuo to provide 5.9 g of amino-(4-hydroxy-phenyl)-acetic acid methyl ester as a white solid. Electrospray Mass Spec 182.2 (M+H)+ The reaction was heated to reflux for 5 h The resulting mixture was concentrated in vacuo the residue was diluted with ether The resulting solid was collected by filtration dried in vacuo

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

Procedure: To a 0° solution of 2.50 g (11.48 mmol) of amino-(4-hydroxy-phenyl)-acetic acid methyl ester (from Example 178) in 125 mL of dichloromethane was added 10 mL of N,N-diisopropylethylamine followed by 2.97 g (11.48 mmol) of 9-fluorenylmethyl chlorformate and the resulting mixture was stirred at 0° for 2 h and room temperature for 2 h. The reaction mixture was then concentrated and the residue was diluted with ethyl acetate and water. The organics were washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with ethyl acetate/hexanes (1:3) to provide methyl(2R)-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}(4-hydroxyphenyl)ethanoate as a white solid. Electrospray Mass Spec 404.1 (M+H)+. The reaction mixture was then concentrated the residue was diluted with ethyl acetate and water The organics were washed with water dried over magnesium sulfate filtered concentrated in vacuo The residue was chromatographed on silica gel eluting with ethyl acetate/hexanes (1:3)

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

Procedure: To 50 mL of methanol cooled to 0° C. was dropwise added 3.75 mL of thionyl chloride followed by 5.0 g (0.030 mmol) of D-4-hydroxyphenylglycine. The reaction was heated to reflux for 5 h then stirred overnight at room temperature. The resulting mixture was concentrated in vacuo and the residue was diluted with ether. The resulting solid was collected by filtration and dried in vacuo to provide 5.9 g of amino-(4-hydroxy-phenyl)-acetic acid methyl ester as a white solid. Electrospray Mass Spec 182.2 (M+H)+. The reaction was heated to reflux for 5 h The resulting mixture was concentrated in vacuo the residue was diluted with ether The resulting solid was collected by filtration dried in vacuo