反应详情

D-Alanine (20 g, 0.225 mole) was dissolved in dimethylformamide (400 ml), treated with chlorotrimethylsilane (26.8 g, 0.250 mole) and the mixture stirred at room temperature until a homogeneous solution was obtained (approx. 45 minutes). Meanwhile, Nα -benzyloxycarbonyl-β-benzyl-L-aspartic acid (72 g, 0.200 mole) was dissolved in a 1:1 mixture of dimethylformamide and tetrahydrofuran (880 ml), cooled to a -15° C. and treated with N-methylmorpholine (22.4 ml, 0.200 mole) and isobutyl chloroformate (26.2 ml, 0.200 mole). After 8 minutes' activation at -15° C. the precooled solution of D-alanine silyl ester from above was added, followed by the dropwise addition of N-methylmorpholine (22.4 ml, 0.200 mole), ensuring that the temperature of the reaction mixture was maintained at -15° C. The solution was allowed to warm to room temperature slowly and stirred for several hours before acidifying to pH 1-2 (with cooling) using aqueous hydrochloric acid. Chloroform was added, the phases separated and the aqueous layer re-extracted with chloroform. The combined organic extracts were washed with 1N hydrochloric acid (3×), saturated aqueous sodium chloride and dried (MgSO4). After evaporation of the solvent under reduced pressure, the oily residue was triturated with ether. The resulting solid was filtered and dried in vacuo to give Nα -benzyloxycarbonyl-β-benzyl-L-aspartyl-D-alanine (67 g), m.p. 158°-159° C., which was homogeneous by TLC.

1. customwas obtained (approx. 45 minutes)
2. temperaturecooled to a -15° C.
3. temperaturewas maintained at -15° C
4. temperatureto warm to room temperature slowly
5. stirringstirred for several hours
6. temperaturebefore acidifying to pH 1-2 (with cooling)
7. customthe phases separated
8. extractionthe aqueous layer re-extracted with chloroform
9. washThe combined organic extracts were washed with 1N hydrochloric acid (3×), saturated aqueous sodium chloride
10. dry with materialdried (MgSO4)
11. customAfter evaporation of the solvent under reduced pressure
12. customthe oily residue was triturated with ether
13. filtrationThe resulting solid was filtered
14. customdried in vacuo