Ethyl Acetate → N-(Trifluoroacetyl)-L-Asp-L-Phe-OMe

HRID 1464211Notes

Reaction equation

HRID 1464211 reaction equation
C(OCC)(=O)C.[F:7][C:8]([F:20])([F:19])[C:9]([NH:11][C@@H:12]1[C:17](=[O:18])[O:16][C:14](=[O:15])[CH2:13]1)=[O:10].C([O-])(=O)C.[Na+].Cl.[CH3:27][O:28][C:29](=[O:39])[C@H:30]([CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[NH2:31]>>[CH3:27][O:28][C:29](=[O:39])[C@H:30]([CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[NH:31][C:17](=[O:18])[C@H:12]([CH2:13][C:14](=[O:15])[OH:16])[NH:11][C:9](=[O:10])[C:8]([F:20])([F:19])[F:7]

Participants

5

Reactant 4

HCID 8857Ethyl AcetateHCID 75736Methyl L-phenylalaninate hydrochlorideHCID 517045Sodium AcetateHCID 12197622(S)-(-)-2-(Trifluoroacetamido)succinic anhydride

Product 1

HCID 14651051N-(Trifluoroacetyl)-L-Asp-L-Phe-OMeYield 78.5%

Procedure

In 84.4 g of ethyl acetate 21.1 g (0.1 mole) of N-trifluoroacetyl-L-aspartic anhydride was suspended, and 9.2 g (0.11 mole) of sodium acetate was added at -5 - 0° C. with stirring, and 21.6 g (0.1 mole) of L-phenylalanine methyl ester hydrochloride was added at the same temperature. The mixture was reacted for 3 hours with stirring at the same temperature and concentrated under reduced pressure. Thereafter 63.3 g of acetic acid was added and stirred for an hour at 15°-20° C. Precipitated crystals were filtered, washed and dried. Crystals of N-trifluoroacetyl-α-L-aspartyl-L-phenylalanine methyl ester were obtained in a yield of 30.6 g (78.5% yield on L-phenylalanine methyl ester hydrochloride). The crystals obtained were analyzed by high performance liquid chromatography to give a ratio of α-isomer:β-isomer of 99.0:1.0.

Workup

  1. customThe mixture was reacted for 3 hours
  2. stirringwith stirring at the same temperature
  3. concentrationconcentrated under reduced pressure
  4. additionThereafter 63.3 g of acetic acid was added
  5. stirringstirred for an hour at 15°-20° C
  6. customPrecipitated crystals
  7. filtrationwere filtered
  8. washwashed
  9. customdried

Sources & evidence

ORD record
ord-fe78540233ae49969e012c012092c062
Source dataset
uspto-grants-1994_04
Patent number
US05302743

Reaction notes

Loading…