(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanedioic acid

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

Procedure: A suspension of Boc-Asp-OH (8.11 mmol) and fluoroacetic anhydride (16.2 mmol) in benzene (30 ml) was treated with triethylamine (16.2 mmol) at room temperature. The catalyst 4-dimethylaminopyridine (0.41 mmol) was added to the solution and the reaction stirred for about 2 h at room temperature. About 100 ml benzene was added to the reaction mixture. The organic solution was washed with 1N HCl (2×50 ml), saturated NaHCO3 (2×50 ml), and saturated NaCl (2×50 ml), followed by drying over anhydrous MgSO4. The solvent was then removed by evaporation under reduced pressure. The resulting oil was applied to a 2.5×80 cm column of silica gel (60-200 mesh). The title compound was eluded with 2% methanol in chloroform. The organic solution was washed with 1N HCl (2×50 ml), saturated NaHCO3 (2×50 ml), and saturated NaCl (2×50 ml) by drying over anhydrous MgSO4 The solvent was then removed by evaporation under reduced pressure

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

Procedure: N-(t-butoxycarbonyl)-L-aspartic acid is coupled with two equivalents of β-alanine benzyl ester to give N,N'-[[(S)-(1-t-butoxyformamido)ethylene]dicarbonyl]di-β-alanine dibenzyl ester, m.p. 109°-110° C.

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

Procedure: To a solution of 23.3 g N-t-butyloxycarbonyl-L-aspartic acid in 150 mL of tetrahydrofuran was added portionwise 20.6 g of N,N-dicyclohexyl-carbodiimide at 0° C. and overnight at room temperature. The precipitated dicyclohexyl urea was filtered off and all solvent was evaporated under reduced pressure. The oily residue was crystallized from acetone/hexane to give 18.24 g of anydride as white needles. overnight at room temperature The precipitated dicyclohexyl urea was filtered off all solvent was evaporated under reduced pressure The oily residue was crystallized from acetone/hexane to give 18.24 g of anydride as white needles

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

Procedure: To a solution of 23.3 g N-t-butyloxycarbonyl-L-aspartic acid in 150 mL of tetrahydrofuran was added portionwise 20.6 g of N,N-dicyclohexyl-carbodiimide at 0° C. and overnight at room temperature. The precipitated dicyclohexyl urea was filtered off and all solvent was evaporated under reduced pressure. The oily residue was crystallized from acetone/hexane to give 18.24 g of anydride as white needles. overnight at room temperature The precipitated dicyclohexyl urea was filtered off all solvent was evaporated under reduced pressure The oily residue was crystallized from acetone/hexane to give 18.24 g of anydride as white needles

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

Procedure: A suspension of Boc-Asp-OH (8.11 mmol) and fluoroacetic anhydride (16.2 mmol) in benzene (30 ml) was treated with triethylamine (16.2 mmol) at room temperature. The catalyst 4-dimethylaminopyridine (0.41 mmol) was added to the solution and the reaction stirred for about 2 h at room temperature. About 100 ml benzene was added to the reaction mixture. The organic solution was washed with 1N HCl (2×50 ml), saturated NaHCO3 (2×50 ml), and saturated NaCl (2×50 ml), followed by drying over anhydrous MgSO4. The solvent was then removed by evaporation under reduced pressure. The resulting oil was applied to a 2.5×80 cm column of silica gel (60-200 mesh). The title compound was eluded with 2% methanol in chloroform. The organic solution was washed with 1N HCl (2×50 ml), saturated NaHCO3 (2×50 ml), and saturated NaCl (2×50 ml) by drying over anhydrous MgSO4 The solvent was then removed by evaporation under reduced pressure

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

Procedure: A suspension of Boc-Asp-OH (8.11 mmol) and fluoroacetic anhydride (16.2 mmol) in benzene (30 ml) was treated with triethylamine (16.2 mmol) at room temperature. The catalyst 4-dimethylaminopyridine (0.41 mmol) was added to the solution and the reaction stirred for about 2 h at room temperature. About 100 ml benzene was added to the reaction mixture. The organic solution was washed with 1N HCl (2×50 ml), saturated NaHCO3 (2×50 ml), and saturated NaCl (2×50 ml), followed by drying over anhydrous MgSO4. The solvent was then removed by evaporation under reduced pressure. The resulting oil was applied to a 2.5×80 cm column of silica gel (60-200 mesh). The title compound was eluded with 2% methanol in chloroform. The organic solution was washed with 1N HCl (2×50 ml), saturated NaHCO3 (2×50 ml), and saturated NaCl (2×50 ml) by drying over anhydrous MgSO4 The solvent was then removed by evaporation under reduced pressure

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

Procedure: N-(t-butoxycarbonyl)-L-aspartic acid is coupled with two equivalents of β-alanine benzyl ester to give N,N'-[[(S)-(1-t-butoxyformamido)ethylene]dicarbonyl]di-β-alanine dibenzyl ester, m.p. 109°-110° C.

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

Procedure: N-(t-butoxycarbonyl)-L-aspartic acid is coupled with two equivalents of β-alanine benzyl ester to give N,N'-[[(S)-(1-t-butoxyformamido)ethylene]dicarbonyl]di-β-alanine dibenzyl ester, m.p. 109°-110° C.

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

Procedure: A suspension of Boc-Asp-OH (8.11 mmol) and fluoroacetic anhydride (16.2 mmol) in benzene (30 ml) was treated with triethylamine (16.2 mmol) at room temperature. The catalyst 4-dimethylaminopyridine (0.41 mmol) was added to the solution and the reaction stirred for about 2 h at room temperature. About 100 ml benzene was added to the reaction mixture. The organic solution was washed with 1N HCl (2×50 ml), saturated NaHCO3 (2×50 ml), and saturated NaCl (2×50 ml), followed by drying over anhydrous MgSO4. The solvent was then removed by evaporation under reduced pressure. The resulting oil was applied to a 2.5×80 cm column of silica gel (60-200 mesh). The title compound was eluded with 2% methanol in chloroform. The organic solution was washed with 1N HCl (2×50 ml), saturated NaHCO3 (2×50 ml), and saturated NaCl (2×50 ml) by drying over anhydrous MgSO4 The solvent was then removed by evaporation under reduced pressure

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

Procedure: To a solution of 1.33 g (10 mmol) of L-aspartic acid in a dioxane/water (1:1) mixture (30 ml), 4.2 ml (30 mmol) of triethylamine are added, and the mixture is stirred until solution is complete (approximately 10 min). 2.85 g (10 mmol) of tert-butyl 1,2,2,2-tetrachloroethyl carbonate are then added and the mixture is stirred for 6 hours at 20° C. 50 ml of water are then added and the mixture is extracted with 2×20 ml of ethyl acetate. The aqueous phase is acidified (pH 2-3) with NHCl, and then extracted with 3×30 ml of ethyl acetate. The extract is washed with saturated NaCl solution, dried over MgSO4 and evaporated. The product obtained is crystallised in ethyl acetate and petroleum ether. 1.4 g (60% yield) of the expected acid is obtained. ##STR60## (approximately 10 min) the mixture is stirred for 6 hours at 20° C the mixture is extracted with 2×20 ml of ethyl acetate extracted with 3×30 ml of ethyl acetate The extract is washed with saturated NaCl solution dried over MgSO4 evaporated The product obtained is crystallised in ethyl acetate

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

Procedure: A suspension of Boc-Asp-OH (8.11 mmol) and fluoroacetic anhydride (16.2 mmol) in benzene (30 ml) was treated with triethylamine (16.2 mmol) at room temperature. The catalyst 4-dimethylaminopyridine (0.41 mmol) was added to the solution and the reaction stirred for about 2 h at room temperature. About 100 ml benzene was added to the reaction mixture. The organic solution was washed with 1N HCl (2×50 ml), saturated NaHCO3 (2×50 ml), and saturated NaCl (2×50 ml), followed by drying over anhydrous MgSO4. The solvent was then removed by evaporation under reduced pressure. The resulting oil was applied to a 2.5×80 cm column of silica gel (60-200 mesh). The title compound was eluded with 2% methanol in chloroform. The organic solution was washed with 1N HCl (2×50 ml), saturated NaHCO3 (2×50 ml), and saturated NaCl (2×50 ml) by drying over anhydrous MgSO4 The solvent was then removed by evaporation under reduced pressure

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

Procedure: To a solution of 1.33 g (10 mmol) of L-aspartic acid in a dioxane/water (1:1) mixture (30 ml), 4.2 ml (30 mmol) of triethylamine are added, and the mixture is stirred until solution is complete (approximately 10 min). 2.85 g (10 mmol) of tert-butyl 1,2,2,2-tetrachloroethyl carbonate are then added and the mixture is stirred for 6 hours at 20° C. 50 ml of water are then added and the mixture is extracted with 2×20 ml of ethyl acetate. The aqueous phase is acidified (pH 2-3) with NHCl, and then extracted with 3×30 ml of ethyl acetate. The extract is washed with saturated NaCl solution, dried over MgSO4 and evaporated. The product obtained is crystallised in ethyl acetate and petroleum ether. 1.4 g (60% yield) of the expected acid is obtained. ##STR60## (approximately 10 min) the mixture is stirred for 6 hours at 20° C the mixture is extracted with 2×20 ml of ethyl acetate extracted with 3×30 ml of ethyl acetate The extract is washed with saturated NaCl solution dried over MgSO4 evaporated The product obtained is crystallised in ethyl acetate