Water → Z-Phe-Gly-Leu-OH

HRID 236457

Reaction equation

HRID 236457 reaction equation
[NH:1]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@H:2]([C:10]([OH:12])=O)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[NH2:23][CH2:24][C:25]([NH:27][C@H:28]([C:33]([OH:35])=[O:34])[CH2:29][CH:30]([CH3:32])[CH3:31])=[O:26].C(N(CC)CC)C.O>O1CCOCC1>[NH:1]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@H:2]([C:10]([NH:23][CH2:24][C:25]([NH:27][C@H:28]([C:33]([OH:35])=[O:34])[CH2:29][CH:30]([CH3:32])[CH3:31])=[O:26])=[O:12])[CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 70878Benzyloxycarbonyl-L-phenylalanineHCID 92843Glycyl-L-leucine

Product 1

HCID 131715018Z-Phe-Gly-Leu-OHYield 73.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

The N-hydroxysuccinimide ester of Z-Phe-OH (19.15 g, 48.3 mmol) was dissolved in 50 mL of dioxane and the resulting solution was filtered into a solution consisting of H-Gly-Leu-OH (10.0 g, 53.1 mmol), triethylamine (10.1 mL, 72.4 mmol), and water (50 mL). This reaction mixture was stirred overnight at about 23°, and then concentrated approximately 60% by evaporation. The resulting concentrated solution was diluted with 1.0N hydrochloric acid until acidic. Product Z-Phe-Gly-Leu-OH was extracted into ethyl acetate, and the resulting extract was washed with 0.2N hydrochloric acid, followed by saturated aqueous sodium chloride adjusted to 0.10N hydrochloric acid. After washing, the ethyl acetate solution was dried over anhydrous sodium sulfate and filtered. The ethyl acetate was then evaporated to yield 22.5 g of a white, foamy product, which was subsequently crystallized from ethyl acetate to yield 16.7 g of Z-Phe-Gly-Leu-OH (m.p. 147°-148°).

Workup

  1. filtrationthe resulting solution was filtered into a solution
  2. concentrationconcentrated approximately 60%
  3. customby evaporation
  4. additionThe resulting concentrated solution was diluted with 1.0N hydrochloric acid until acidic
  5. extractionProduct Z-Phe-Gly-Leu-OH was extracted into ethyl acetate
  6. extractionthe resulting extract
  7. washwas washed with 0.2N hydrochloric acid
  8. washAfter washing
  9. dry with materialthe ethyl acetate solution was dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. customThe ethyl acetate was then evaporated
  12. customto yield 22.5 g of a white, foamy product, which
  13. customwas subsequently crystallized from ethyl acetate

Sources & evidence

ORD record
ord-a0521274689e4da7b3dba97f0b6cf983
Source dataset
uspto-grants-1987_02
Patent number
US04644055

Linked notes

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