N-[(3S)-2,5-dioxooxolan-3-yl]acetamide

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred suspension of sodium borohydride (1.264 g, 33.41 mmol) in tetrahydrofuran (100 mL), N-acetyl-L-aspartic anhydride (5.0 g, 31.82 mmol, prepared as described in example A) was added in five portions at 0° C. over 1 h. The white suspension was warmed to room temperature, stirred for 3 h and cooled again to 0° C. Cold water (˜50 mL) was slowly added to the stirred mixture while the temperature was allowed to reach 15° C. After stirring overnight at room temperature, tetrahydrofuran was evaporated in vacuo. The residual aqueous solution was diluted with water to a volume of 100 mL and passed through a Dowex 50X8 ion exchange column (100 g). The ion exchange column was rinsed with water (3×100 mL). The resulting aqueous solution was concentrated in vacuo and the residue was taken up in a mixture of toluene (30 mL) and methanol (70 mL). The solvent was evaporated in vacuo. This procedure was repeated, i.e. the residue was taken up in toluene-methanol and concentrated again another three times. The remaining colorless oil (5.4 g) which consisted of a mixture of hydroxy-acid and lactone was dissolved in acetic acid (54 mL). Toluene (54 mL) was added and the solution was stirred at 110° C. for 2.5 h. After this time, all hydroxy-acid was cyclized to the desired lactone according to GC analysis of a reaction sample which had been concentrated and silylated. The reaction mixture was concentrated in vacuo. Three times the residue was taken up in toluene and concentrated again to give the crude product (4.2 g) as a white solid. For purification, the crude product was dissolved in acetonitrile (30 mL). Toluene (60 mL) was added to the solution and acetonitrile was partly removed from the mixture in vacuo, until the product started to crystallize. The product was collected by filtration, washed with toluene and tert-butyl methyl ether and dried in vacuo to afford (S)-N-(5-oxo-tetrahydro-furan-3-yl)-acetamide (3.8 g, 83% based on N-acetyl-L-aspartic anhydride) as white crystals. The structure of the compound was confirmed by 1H-NMR, MS, IR. and elemental analysis. was added in five portions at 0° C. over 1 h cooled again to 0° C to reach 15° C After stirring overnight at room temperature tetrahydrofuran was evaporated in vacuo The residual aqueous solution was diluted with water to a volume of 100 mL The ion exchange column was rinsed with water (3×100 mL) The resulting aqueous solution was concentrated in vacuo the residue was taken up in a mixture of toluene (30 mL) and methanol (70 mL) The solvent was evaporated in vacuo concentrated again another three times The remaining colorless oil (5.4 g) which consisted of a mixture of hydroxy-acid and lactone was dissolved in acetic acid (54 mL) Toluene (54 mL) was added the solution was stirred at 110° C. for 2.5 h had been concentrated The reaction mixture was concentrated in vacuo concentrated again to give the crude product (4.2 g) as a white solid For purification the crude product was dissolved in acetonitrile (30 mL) Toluene (60 mL) was added to the solution and acetonitrile was partly removed from the mixture in vacuo, until the product to crystallize The product was collected by filtration washed with toluene and tert-butyl methyl ether dried in vacuo

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred suspension of N-Acetyl-L-aspartic acid (35.0 g, 199.9 mmol) in acetic anhydride (100 mL, 1.06 mol) was heated to 80° C. for ˜1 h until all the solid material had dissolved. The heating bath was removed, and the reaction mixture was stirred 4 h at ambient temperature. The product was collected by filtration and washed with tert-butyl methyl ether to afford N-acetyl-L-aspartic anhydride (27.8 g, 88%) as white crystals, [α]D−49.0° (c=2.5, Ac2O). had dissolved The heating bath was removed The product was collected by filtration washed with tert-butyl methyl ether