ethyl 3-(benzylamino)propanoate

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

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

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

Procedure: The title compound is prepared according to the method of Klioze and Ehrgott (U.S. Pat. No. 4,216,218) from ethyl acrylate and benzylamine.

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

Procedure: The title compound is prepared according to the method of Klioze and Ehrgott (U.S. Pat. No. 4,216,218) from ethyl acrylate and benzylamine.

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

Procedure: To a solution of 1H-benzo[d][1,2,3]triazole (5.46 g, 45.8 mmol) in MeOH (32 mL) at 0° C. were added ethyl 3-(benzylamino)propanoate (10 g, 45.8 mmol) and an aqueous solution of formaldehyde (36%, 4.56 mL, 59.6 mmol). The reaction mixture was warmed to room temperature and stirred for 12 hours. The solvent was evaporated and the residue was purified by flash-chromatography over 330 g flash pack using gradient EtOAc/Heptane 5-50% over 40 minutes. The title compound was obtained as colorless oil (12.62 g, 81%). The solvent was evaporated the residue was purified by flash-chromatography over 330 g flash pack over 40 minutes

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

Procedure: To a solution of 1H-benzo[d][1,2,3]triazole (5.46 g, 45.8 mmol) in MeOH (32 mL) at 0° C. were added ethyl 3-(benzylamino)propanoate (10 g, 45.8 mmol) and an aqueous solution of formaldehyde (36%, 4.56 mL, 59.6 mmol). The reaction mixture was warmed to room temperature and stirred for 12 hours. The solvent was evaporated and the residue was purified by flash-chromatography over 330 g flash pack using gradient EtOAc/Heptane 5-50% over 40 minutes. The title compound was obtained as colorless oil (12.62 g, 81%). The solvent was evaporated the residue was purified by flash-chromatography over 330 g flash pack over 40 minutes

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

Procedure: The title compound is prepared according to the method of Klioze and Ehrgott (U.S. Pat. No. 4,216,218) from ethyl acrylate and benzylamine.

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

Procedure: This compound is prepared according to the method of Klioze and Ehrgott (U.S. Pat. No. 4,216,218) from ethyl acrylate and benzylamine This compound is prepared

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

Procedure: This compound is prepared according to the method of Klioze and Ehrgott (U.S. Pat. No. 4,216,218) from ethyl acrylate and benzylamine This compound is prepared

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

Procedure: To a solution of 1H-benzotriazole (2.38 g) in methanol (20 mL) were added ethyl N-benzyl-β-alaninate (4.14 g) and aqueous formaldehyde solution (37%, 2 mL) at room temperature. The reaction mixture was stirred overnight at room temperature, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/petroleum ether) to give ethyl N-(1H-benzotriazol-1-ylmethyl)-N-benzyl-β-alaninate (5.60 g). To a mixture of zinc powder (1.74 g) in anhydrous THF (16 mL) was added chlorotrimethylsilane (1.58 g) under nitrogen atmosphere, and the mixture was stirred at room temperature for 10 min. To the reaction mixture was added ethyl bromodifluoroacetate (2.97 g) at room temperature, and then a solution of ethyl N-(1H-benzotriazol-1-ylmethyl)-N-benzyl-β-alaninate (4.50 g) in THF (8 mL) was added thereto at room temperature. The reaction mixture was stirred at room temperature for 18 hr, and added to water. The insoluble substance was removed by the filtration, and the filtrate was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/petroleum ether) to give the title compound (3.23 g). concentrated under reduced pressure The residue was purified by silica gel chromatography (ethyl acetate/petroleum ether)

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

Procedure: To a solution of 1H-benzotriazole (2.38 g) in methanol (20 mL) were added ethyl N-benzyl-β-alaninate (4.14 g) and aqueous formaldehyde solution (37%, 2 mL) at room temperature. The reaction mixture was stirred overnight at room temperature, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/petroleum ether) to give ethyl N-(1H-benzotriazol-1-ylmethyl)-N-benzyl-β-alaninate (5.60 g). To a mixture of zinc powder (1.74 g) in anhydrous THF (16 mL) was added chlorotrimethylsilane (1.58 g) under nitrogen atmosphere, and the mixture was stirred at room temperature for 10 min. To the reaction mixture was added ethyl bromodifluoroacetate (2.97 g) at room temperature, and then a solution of ethyl N-(1H-benzotriazol-1-ylmethyl)-N-benzyl-β-alaninate (4.50 g) in THF (8 mL) was added thereto at room temperature. The reaction mixture was stirred at room temperature for 18 hr, and added to water. The insoluble substance was removed by the filtration, and the filtrate was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/petroleum ether) to give the title compound (3.23 g). concentrated under reduced pressure The residue was purified by silica gel chromatography (ethyl acetate/petroleum ether)

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

Procedure: A solution of 1.04 g (0.005 mole) of 3-benzylamino-propanoic acid ethyl ester in 20 mL of water was added dropwise to a solution of 0.97 g (0.005 mole) of 2,4-dichloro-5-nitro-pyrimidine in 20 mL of ethyl ether. At 0 degrees, 1.0 g (0.010 mole) of potassium bicarbonate was added. The mixture was stirred at ambient temperature for 3 hours. The layers were then separated, and the aqueous layer extracted twice with 30 mL of ether. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with hexanes-ethyl acetate (100:0-90:10) gave 1.70 g of 3-[benzyl-(2-chloro-5-nitro-pyrimidin-4-yl)-amino]-propanoic acid ethyl ester (IV-22). The layers were then separated the aqueous layer extracted twice with 30 mL of ether The combined organic layers were dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure Purification by silica gel chromatography eluting with hexanes-ethyl acetate (100:0-90:10)