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

HRID 1462114Notes

Reaction equation

HRID 1462114 reaction equation
C([CH2:8][C@H:9]([NH2:13])[C:10]([OH:12])=[O:11])C[C@@H](N)C(O)=O.NC[C:16]([OH:18])=[O:17].CN1CC[O:23][CH2:22][CH2:21]1.[CH2:26](OC(Cl)=O)[CH:27]([CH3:29])[CH3:28].C[Si]([CH:38]([Si](C)(C)C)[C:39]([NH2:41])=[O:40])(C)C>C(Cl)Cl.CN(C)C=O.C(OCC)(=O)C>[NH:13]([C:16]([O:18][C:27]([CH3:26])([CH3:28])[CH3:29])=[O:17])[C@@H:9]([C:10]([O:12][N:41]1[C:22](=[O:23])[CH2:21][CH2:38][C:39]1=[O:40])=[O:11])[CH3:8]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 11708267BistrimethylsilylacetamidHCID 87968512meso-DAP (D)GlyOH

Product 1

HCID 11580086N-[(1,1-Dimethylethoxy)carbonyl]-D-alanine 2,5-dioxo-1-pyrrolidinyl ester

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

D-Lac(oAc)-L-Phe-D-GluoBzl (2) (1.0 g) was dissolved in methylene chloride (40 ml) and N-methylmorpholine (200 mg) was added thereto. To this stirred solution cooled at -10° C. in an ice salt-bath, isobutylchlorocarbonate (270 mg) was added and the mixture was allowed to react at the same temperature for 20 minutes. To the reaction mixture was added the silyl ester prepared from Boc-(D)-mesoDAP-(D)-NHNHBoc-(L)-GlyOH (1) (920 mg) in a mixture of methylene chloride (20 ml) and dimethylformamide (10 ml) containing bis(trimethylsilyl)acetamide (2 ml). The reaction mixture was stirred for 2 hours and concentrated under reduced pressure to give an oily residue which was dissolved in ethyl acetate and washed with 2% hydrochloric acid. The organic layer was washed successively with water and saturated sodium chloride and then dried. Evaporation of the solvent gave a residue which was throughly washed with ether and collected by filtration to give D-Lac(oAc)-L-Phe-γ-D-Glu(α-oBzl)-(L)-Boc-(D)-mesoDAP-(D)-NHNHBoc-(L)-GlyOH (3) (1.660 g).

Workup

  1. customto react at the same temperature for 20 minutes
  2. concentrationconcentrated under reduced pressure
  3. customto give an oily residue which
  4. washwashed with 2% hydrochloric acid
  5. washThe organic layer was washed successively with water and saturated sodium chloride
  6. customdried
  7. customEvaporation of the solvent
  8. customgave a residue which
  9. washwas throughly washed with ether
  10. filtrationcollected by filtration

Sources & evidence

ORD record
ord-cb26e0b02ad344d7918596c4f3578377
Source dataset
uspto-grants-1984_07
Patent number
US04458078

Reaction notes

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