methyl 2-(3-phenylprop-2-enoylamino)acetate

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the same general procedure described previously for cinnamoyl-glycine-methyl ester, glycine-t-butyl ester. MCl (10.88 grams) was dissolved in dimethyl formamide (approximately 100 ml), cooled to 0° C. and treated with N-methylmorpholine (9.04 ml, 1 equivalent) followed immediately by a pre-cooled solution of benzoic acid (7.94 grams) in ethyl acetate (approximately 75 ml) which had been pre-activated by treatment with N-methylmorpholine (9.04 ml) followed by isobutyl chloroformate (8.4 ml) at -20° C. After work-up, benzoyl-glycine-t-butyl ester was obtained as a white solid which was used for the next step without further purification.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the same general procedure described previously for cinnamoyl-glycine-methyl ester, glycine-t-butyl ester. MCl (10.88 grams) was dissolved in dimethyl formamide (approximately 100 ml), cooled to 0° C. and treated with N-methylmorpholine (9.04 ml, 1 equivalent) followed immediately by a pre-cooled solution of benzoic acid (7.94 grams) in ethyl acetate (approximately 75 ml) which had been pre-activated by treatment with N-methylmorpholine (9.04 ml) followed by isobutyl chloroformate (8.4 ml) at -20° C. After work-up, benzoyl-glycine-t-butyl ester was obtained as a white solid which was used for the next step without further purification.

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

Procedure: Cinnamic acid (38.0 g) was coupled to glycine methyl ester hydrochloride in dimethylformamide by treatment with dicyclohexylcarbodiimide (52.84 g) and 1-hydroxybenzotriazole (39.24 g), followed by N-methylmorpholine (37.56 ml). The reaction mixture was stirred overnight at room temperature and then worked up in the usual manner to give the desired product.

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

Procedure: Cinnamic acid (38.0 g) was coupled to glycine methyl ester hydrochloride in dimethylformamide by treatment with dicyclohexylcarbodiimide (52.84 g) and 1-hydroxybenzotriazole (39.24 g), followed by N-methylmorpholine (37.56 ml). The reaction mixture was stirred overnight at room temperature and then worked up in the usual manner to give the desired product.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the general procedure described in example 1, step 2, for cinnamoyl-glycine methyl ester, glycine methyl ester hydrochloride (7.5 g) was suspended in tetrahydrofuran, cooled to 0° C., treated with N-methylmorpholine (8.4 ml, 1 equivalent), followed immediately by a precooled solution of 4-fluorocinnamic acid (10.0 g) in tetrahydrofuran, which had been pre-activated by treatment with dicyclohexylcarbodiimide (12.4 g, 1 equivalent) and 1-hydroxybenzotriazole (9.2 g). After work-up, 4-fluorocinnamoyl-glycine methyl ester was obtained as a white solid which was used for the next step without further purification.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the general procedure described in example 1, step 2, for cinnamoyl-glycine methyl ester, glycine methyl ester hydrochloride (7.5 g) was suspended in tetrahydrofuran, cooled to 0° C., treated with N-methylmorpholine (8.4 ml, 1 equivalent), followed immediately by a precooled solution of 4-fluorocinnamic acid (10.0 g) in tetrahydrofuran, which had been pre-activated by treatment with dicyclohexylcarbodiimide (12.4 g, 1 equivalent) and 1-hydroxybenzotriazole (9.2 g). After work-up, 4-fluorocinnamoyl-glycine methyl ester was obtained as a white solid which was used for the next step without further purification.

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

Procedure: Glycine methyl ester hydrochloride was suspended in tetrahydrofuran, the suspension was cooled to -5° C. to -10° C., and then half of the N-methylmorpholine was added. Cinnamoyl chloride was added immediately, followed by the other half of the N-methylmorpholine. The reaction mixture was stirred for 30 minutes at low temperature, then it was allowed to warm to room temperature and stirring was continued for 2 to 3 hours. After being diluted with ethyl acetate (about 750 ml) the solution was washed with water (three times), an aqueous solution of 0.5 N hydrochloric acid (three times) and finally with water. The organic phase was dried over magnesium sulfate, filtered and evaporated to dryness under reduced pressure. The residue was triturated with petroleum ether is order to induce crystallization. The product was left to stand for about 14 hours at 4° C., then it was filtered off and dried in a vacuum. It was used in the next step without further purification. 31 g of product were obtained. the suspension was cooled to -5° C. to -10° C. stirring was continued for 2 to 3 hours was washed with water (three times) The organic phase was dried over magnesium sulfate filtered evaporated to dryness under reduced pressure The residue was triturated with petroleum ether crystallization The product was left to stand for about 14 hours at 4° C. it was filtered off dried in a vacuum It was used in the next step without further purification

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

Procedure: Glycine methyl ester hydrochloride was suspended in tetrahydrofuran, the suspension was cooled to -5° C. to -10° C., and then half of the N-methylmorpholine was added. Cinnamoyl chloride was added immediately, followed by the other half of the N-methylmorpholine. The reaction mixture was stirred for 30 minutes at low temperature, then it was allowed to warm to room temperature and stirring was continued for 2 to 3 hours. After being diluted with ethyl acetate (about 750 ml) the solution was washed with water (three times), an aqueous solution of 0.5 N hydrochloric acid (three times) and finally with water. The organic phase was dried over magnesium sulfate, filtered and evaporated to dryness under reduced pressure. The residue was triturated with petroleum ether is order to induce crystallization. The product was left to stand for about 14 hours at 4° C., then it was filtered off and dried in a vacuum. It was used in the next step without further purification. 31 g of product were obtained. the suspension was cooled to -5° C. to -10° C. stirring was continued for 2 to 3 hours was washed with water (three times) The organic phase was dried over magnesium sulfate filtered evaporated to dryness under reduced pressure The residue was triturated with petroleum ether crystallization The product was left to stand for about 14 hours at 4° C. it was filtered off dried in a vacuum It was used in the next step without further purification

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the same general procedure described previously for cinnamoyl-glycine-methyl ester, glycine-t-butyl ester. MCl (10.88 grams) was dissolved in dimethyl formamide (approximately 100 ml), cooled to 0° C. and treated with N-methylmorpholine (9.04 ml, 1 equivalent) followed immediately by a pre-cooled solution of benzoic acid (7.94 grams) in ethyl acetate (approximately 75 ml) which had been pre-activated by treatment with N-methylmorpholine (9.04 ml) followed by isobutyl chloroformate (8.4 ml) at -20° C. After work-up, benzoyl-glycine-t-butyl ester was obtained as a white solid which was used for the next step without further purification.

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

Procedure: Cinnamic acid (38.0 g) was coupled to glycine methyl ester hydrochloride in dimethylformamide by treatment with dicyclohexylcarbodiimide (52.84 g) and 1-hydroxybenzotriazole (39.24 g), followed by N-methylmorpholine (37.56 ml). The reaction mixture was stirred overnight at room temperature and then worked up in the usual manner to give the desired product.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the general procedure described in example 1, step 2, for cinnamoyl-glycine methyl ester, glycine methyl ester hydrochloride (7.5 g) was suspended in tetrahydrofuran, cooled to 0° C., treated with N-methylmorpholine (8.4 ml, 1 equivalent), followed immediately by a precooled solution of 4-fluorocinnamic acid (10.0 g) in tetrahydrofuran, which had been pre-activated by treatment with dicyclohexylcarbodiimide (12.4 g, 1 equivalent) and 1-hydroxybenzotriazole (9.2 g). After work-up, 4-fluorocinnamoyl-glycine methyl ester was obtained as a white solid which was used for the next step without further purification.