HCID 15384157, compound → HCID 22859271, compound

HRID 1439967Notes

Reaction equation

HRID 1439967 reaction equation
C(O[C:9]([NH:11][C@H:12]([C:20]([NH:22][C@H:23]1[CH2:27][CH2:26][O:25][C:24]1=[O:28])=[O:21])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:10])C1C=CC=CC=1>O1CCCC1.[Pd]>[C:9]([NH:11][C@H:12]([C:20]([NH:22][C@H:23]1[CH2:27][CH2:26][O:25][C:24]1=[O:28])=[O:21])[CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)(=[O:10])[CH:14]([CH2:15][CH2:16][CH3:17])[CH2:13][CH2:12][CH3:20]

Participants

4

Reactant 1

HCID 15384157HCID 15384157, compound

Product 1

HCID 22859271HCID 22859271, compoundYield 74.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

(S)-3-[[N-Benzyloxycarbonyl-(L)-phenylalanyl]amino]tetrahydrofuran-2-one (1.5 g) was dissolved in tetrahydrofuran (35 ml) followed by addition of palladium-on-carbon (5%, 0.8 g) and the catalytic hydrogenation was carried out at room temperature and atmospheric pressure. The catalyst was then filtered off and the filtrate was concentrated under reduced pressure. The residue was dissolved in N,N-dimethylformamide (DMF) (35 ml). Then, valproic acid [(C3H7)2CHCOOH](0.622 g) and 1-hydroxybenzotriazole (HOBt) (0.66 g) were added, after which 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSCD.HCl) (0.902 g) was added under ice-cooling and the whole mixture was stirred at room temperature for 14 hours. The reaction mixture was then poured into ice-water and extracted with ethyl acetate. The ethyl acetate layer was washed with 10% aqueous citric acid, water, saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride in the order mentioned and dried (MgSO4) and the solvent was distilled off to give (S)-3-[[N-valproyl-(L)-phenylalanyl]amino]tetrahydrofuran-2-one (chemical formula below) (0.55 g, 38%). This product was recrysallized from dichloromethane-ether. Colorless prisms, m.p. 203°-205° C. Optical rotation [α]D -39.3° (c=0.52, CHCl3). ##STR32##

Workup

  1. customwas carried out at room temperature
  2. filtrationThe catalyst was then filtered off
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in N,N-dimethylformamide (DMF) (35 ml)
  5. additionThen, valproic acid [(C3H7)2CHCOOH](0.622 g) and 1-hydroxybenzotriazole (HOBt) (0.66 g) were added
  6. additionafter which 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSCD.HCl) (0.902 g) was added under ice-
  7. temperaturecooling
  8. additionThe reaction mixture was then poured into ice-water
  9. extractionextracted with ethyl acetate
  10. washThe ethyl acetate layer was washed with 10% aqueous citric acid, water, saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride in the order
  11. dry with materialdried (MgSO4)
  12. distillationthe solvent was distilled off

Sources & evidence

ORD record
ord-48e46b14cbed47ddadb8ce6974dc8109
Source dataset
uspto-grants-1996_03
Patent number
US05496834

Reaction notes

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