4-Methylmorpholine → N-[(1,1-Dimethylethoxy)carbonyl]-D-alanine 2,5-dioxo-1-pyrrolidinyl ester

Temperature

-40 °C

To a mixture of D-Lac(OAc)-L-Ala-D-GluOBzl (2) (1.20 g) and N-methylmorpholine (0.28 ml) in methylene chloride (17 ml) was added isobutyl chlorocarbonate (0.33 ml). The resulting mixture was stirred at -15° C. to -10° C. for 30 minutes and then cooled to -40° C. To the resulting mixture was added a mixture of Z-D-LysOH (1) (725 ml) and bis(trimethylsilyl)acetamide (3 ml) in dimethylformamide (3 ml) and methylene chloride (8 ml) at -40° C. The resulting mixture was stirred at -15° C. to -10° C. for an hour and gradually allowed to warm to ambient temperature. The resulting mixture was concentrated, taken up into ethyl acetate (80 ml) and washed with dil hydrochloric acid, water and brine, in turn. The concentrate was dried over magnesium sulfate and the solvent was distilled off to give an oil which was crystallized from a mixture of chloroform and isopropyl ether to give D-Lac(OAc)-L-Ala-γ-D-Glu(α-OBzl)-ε-Z-D-LysOH (3)(1.60 g).

1. additionTo the resulting mixture was added
2. stirringThe resulting mixture was stirred at -15° C. to -10° C. for an hour
3. temperatureto warm to ambient temperature
4. concentrationThe resulting mixture was concentrated
5. washwashed with dil hydrochloric acid, water and brine, in turn
6. dry with materialThe concentrate was dried over magnesium sulfate
7. distillationthe solvent was distilled off
8. customto give an oil which
9. customwas crystallized from a mixture of chloroform and isopropyl ether

ORD record

ord-8d5bb252746a4ca0be44388251b3117c

Source dataset

uspto-grants-1984_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04458078