ethyl 2-(methoxycarbonylamino)acetate

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

Procedure: A mixture of N-carbomethoxy glycine ethyl ester (10.0 g, 0.06 mole), paraformaldehyde (2.0 g, 0.06 mole), acetic anhydride (96%, 4.0 g, 0.06 mole) and acetic acid (20 ml) was stirred for 3 hrs. at 60°-70° C. under nitrogen. Triphenyl phosphite (19.2 g, 0.03 mole) was slowly added then the reaction mixture was refluxed for 2 hrs. at 110°-200° C. The reaction was cooled and the solvent was evaporated under vacuum. The resulting oily material was dissolved in chloroform and washed with water. The product was confirmed by nmr. Yield 70.5%. at 60°-70° C. the reaction mixture was refluxed for 2 hrs at 110°-200° C The reaction was cooled the solvent was evaporated under vacuum The resulting oily material was dissolved in chloroform washed with water

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

Procedure: A mixture of N-carbomethoxy glycine ethyl ester (10.0 g, 0.06 mole), paraformaldehyde (2.0 g, 0.06 mole), acetic anhydride (96%, 4.0 g, 0.06 mole) and acetic acid (20 ml) was stirred for 3 hrs. at 60°-70° C. under nitrogen. Triphenyl phosphite (19.2 g, 0.03 mole) was slowly added then the reaction mixture was refluxed for 2 hrs. at 110°-200° C. The reaction was cooled and the solvent was evaporated under vacuum. The resulting oily material was dissolved in chloroform and washed with water. The product was confirmed by nmr. Yield 70.5%. at 60°-70° C. the reaction mixture was refluxed for 2 hrs at 110°-200° C The reaction was cooled the solvent was evaporated under vacuum The resulting oily material was dissolved in chloroform washed with water

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

Procedure: To a solution of phosgene (70.4 g, 0.71 mole) in dry toluene (300 ml), a mixture of glycine ethyl ester hydrochloride (99.1 g, 0.71 mole) and triethylamine (158 g, 1.56 mole) was slowly added at 0° C. The reaction was exothermic. After 2 hrs. of stirring, anhydrous methanol was added to the reaction mixture and stirring was continued for another 0.5 hrs. The reaction mixture was partitioned between water and chloroform, then the pH of the solution was adjusted to 4 with concentrated HCl. The chloroform layer was dried and the solvent was evaporated to obtain the N-carbomethoxy glycine ethyl ester with the structure being confirmed by spectroscopy. was slowly added at 0° C stirring was continued for another 0.5 hrs The reaction mixture was partitioned between water and chloroform The chloroform layer was dried the solvent was evaporated

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

Procedure: Alternatively, glycine ethyl ester hydrochloride (40.1 g, 0.28 mole) suspended in dry tetrahydrofuran (200 ml) and phosgene were bubbled through the reaction mixture for 0.5 hrs, as the reaction mixture was refluxed. At the end of 0.5 hrs., the reaction was cooled to room temperature and toluene was added followed by the distillation of THF. The reaction mixture containing toluene was further refluxed for 1 hr. The unreacted glycine ethyl ester hydrochloride was filtered and the filtrate containing glycine ethyl ester isocyanate (IR 2250 cm-1) was reacted with excess (2-3 mole) anhydrous methanol and, when the isocyanate peak disappeared, the solvent was removed to isolate N-carbomethoxyglycine ethyl ester. phosgene were bubbled through the reaction mixture for 0.5 hrs, as the reaction mixture was refluxed At the end of 0.5 hrs toluene was added followed by the distillation of THF The reaction mixture containing toluene was further refluxed for 1 hr The unreacted glycine ethyl ester hydrochloride was filtered the filtrate containing glycine ethyl ester isocyanate (IR 2250 cm-1) the solvent was removed

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

Procedure: Alternatively, glycine ethyl ester hydrochloride (40.1 g, 0.28 mole) suspended in dry tetrahydrofuran (200 ml) and phosgene were bubbled through the reaction mixture for 0.5 hrs, as the reaction mixture was refluxed. At the end of 0.5 hrs., the reaction was cooled to room temperature and toluene was added followed by the distillation of THF. The reaction mixture containing toluene was further refluxed for 1 hr. The unreacted glycine ethyl ester hydrochloride was filtered and the filtrate containing glycine ethyl ester isocyanate (IR 2250 cm-1) was reacted with excess (2-3 mole) anhydrous methanol and, when the isocyanate peak disappeared, the solvent was removed to isolate N-carbomethoxyglycine ethyl ester. phosgene were bubbled through the reaction mixture for 0.5 hrs, as the reaction mixture was refluxed At the end of 0.5 hrs toluene was added followed by the distillation of THF The reaction mixture containing toluene was further refluxed for 1 hr The unreacted glycine ethyl ester hydrochloride was filtered the filtrate containing glycine ethyl ester isocyanate (IR 2250 cm-1) the solvent was removed

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

Procedure: A mixture of N-carbomethoxy glycine ethyl ester (10.0 g, 0.06 mole), paraformaldehyde (2.0 g, 0.06 mole), acetic anhydride (96%, 4.0 g, 0.06 mole) and acetic acid (20 ml) was stirred for 3 hrs. at 60°-70° C. under nitrogen. Triphenyl phosphite (19.2 g, 0.03 mole) was slowly added then the reaction mixture was refluxed for 2 hrs. at 110°-200° C. The reaction was cooled and the solvent was evaporated under vacuum. The resulting oily material was dissolved in chloroform and washed with water. The product was confirmed by nmr. Yield 70.5%. at 60°-70° C. the reaction mixture was refluxed for 2 hrs at 110°-200° C The reaction was cooled the solvent was evaporated under vacuum The resulting oily material was dissolved in chloroform washed with water

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

Procedure: To a solution of phosgene (70.4 g, 0.71 mole) in dry toluene (300 ml), a mixture of glycine ethyl ester hydrochloride (99.1 g, 0.71 mole) and triethylamine (158 g, 1.56 mole) was slowly added at 0° C. The reaction was exothermic. After 2 hrs. of stirring, anhydrous methanol was added to the reaction mixture and stirring was continued for another 0.5 hrs. The reaction mixture was partitioned between water and chloroform, then the pH of the solution was adjusted to 4 with concentrated HCl. The chloroform layer was dried and the solvent was evaporated to obtain the N-carbomethoxy glycine ethyl ester with the structure being confirmed by spectroscopy. was slowly added at 0° C stirring was continued for another 0.5 hrs The reaction mixture was partitioned between water and chloroform The chloroform layer was dried the solvent was evaporated

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

Procedure: A mixture of N-carbomethoxy glycine ethyl ester (10.0 g, 0.06 mole), paraformaldehyde (2.0 g, 0.06 mole), acetic anhydride (96%, 4.0 g, 0.06 mole) and acetic acid (20 ml) was stirred for 3 hrs. at 60°-70° C. under nitrogen. Triphenyl phosphite (19.2 g, 0.03 mole) was slowly added then the reaction mixture was refluxed for 2 hrs. at 110°-200° C. The reaction was cooled and the solvent was evaporated under vacuum. The resulting oily material was dissolved in chloroform and washed with water. The product was confirmed by nmr. Yield 70.5%. at 60°-70° C. the reaction mixture was refluxed for 2 hrs at 110°-200° C The reaction was cooled the solvent was evaporated under vacuum The resulting oily material was dissolved in chloroform washed with water

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

Procedure: Alternatively, glycine ethyl ester hydrochloride (40.1 g, 0.28 mole) suspended in dry tetrahydrofuran (200 ml) and phosgene were bubbled through the reaction mixture for 0.5 hrs, as the reaction mixture was refluxed. At the end of 0.5 hrs., the reaction was cooled to room temperature and toluene was added followed by the distillation of THF. The reaction mixture containing toluene was further refluxed for 1 hr. The unreacted glycine ethyl ester hydrochloride was filtered and the filtrate containing glycine ethyl ester isocyanate (IR 2250 cm-1) was reacted with excess (2-3 mole) anhydrous methanol and, when the isocyanate peak disappeared, the solvent was removed to isolate N-carbomethoxyglycine ethyl ester. phosgene were bubbled through the reaction mixture for 0.5 hrs, as the reaction mixture was refluxed At the end of 0.5 hrs toluene was added followed by the distillation of THF The reaction mixture containing toluene was further refluxed for 1 hr The unreacted glycine ethyl ester hydrochloride was filtered the filtrate containing glycine ethyl ester isocyanate (IR 2250 cm-1) the solvent was removed

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

Procedure: Alternatively, glycine ethyl ester hydrochloride (40.1 g, 0.28 mole) suspended in dry tetrahydrofuran (200 ml) and phosgene were bubbled through the reaction mixture for 0.5 hrs, as the reaction mixture was refluxed. At the end of 0.5 hrs., the reaction was cooled to room temperature and toluene was added followed by the distillation of THF. The reaction mixture containing toluene was further refluxed for 1 hr. The unreacted glycine ethyl ester hydrochloride was filtered and the filtrate containing glycine ethyl ester isocyanate (IR 2250 cm-1) was reacted with excess (2-3 mole) anhydrous methanol and, when the isocyanate peak disappeared, the solvent was removed to isolate N-carbomethoxyglycine ethyl ester. phosgene were bubbled through the reaction mixture for 0.5 hrs, as the reaction mixture was refluxed At the end of 0.5 hrs toluene was added followed by the distillation of THF The reaction mixture containing toluene was further refluxed for 1 hr The unreacted glycine ethyl ester hydrochloride was filtered the filtrate containing glycine ethyl ester isocyanate (IR 2250 cm-1) the solvent was removed

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

Procedure: 100 g of ethyl N-methoxycarbonylglycinate were dissolved in 600 ml of N,N-dimethylformamide. Then ice-cooling the mixture, 25 g of sodium hydride (60% oil dispersion) were added thereto under a nitrogen atmosphere. After the reaction mixture was stirred for 2 hours, 81.3 g of propargyl bromide were dropped thereto over 2 hours. After the mixture was further stirred for an hour, the reaction product was poured into water and the aqueous layer was washed with hexane. Then it was subjected to three times of extraction with 100 ml of ether. The ether layers were combined together and dried over anhydrous magnesium sulfate and the solvent was evaporated off to obtain 79.8 g of ethyl N-propargyl-N-methoxycarbonylglycinate. were added over 2 hours After the mixture was further stirred for an hour the aqueous layer was washed with hexane Then it was subjected to three times of extraction with 100 ml of ether dried over anhydrous magnesium sulfate the solvent was evaporated off

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

Procedure: A mixture of N-carbomethoxy glycine ethyl ester (10.0 g, 0.06 mole), paraformaldehyde (2.0 g, 0.06 mole), acetic anhydride (96%, 4.0 g, 0.06 mole) and acetic acid (20 ml) was stirred for 3 hrs. at 60°-70° C. under nitrogen. Triphenyl phosphite (19.2 g, 0.03 mole) was slowly added then the reaction mixture was refluxed for 2 hrs. at 110°-200° C. The reaction was cooled and the solvent was evaporated under vacuum. The resulting oily material was dissolved in chloroform and washed with water. The product was confirmed by nmr. Yield 70.5%. at 60°-70° C. the reaction mixture was refluxed for 2 hrs at 110°-200° C The reaction was cooled the solvent was evaporated under vacuum The resulting oily material was dissolved in chloroform washed with water