Pyridine → 2768-53-8

HRID 1759503Notes

Reaction equation

HRID 1759503 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:14]([OH:16])=O)[CH3:13])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.[NH2:23][C@H:24]([C:32]([OH:34])=[O:33])[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(N(CC)CC)C>C(#N)C.O>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:14]([NH:23][C@H:24]([C:32]([OH:34])=[O:33])[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:16])[CH3:13])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 6140L-PhenylalanineHCID 8471TriethylamineHCID 736104N-carbobenzyloxyalanine2×

Product 1

HCID 69991262768-53-8Yield 91.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Procedure

A solution of 0.223 g (0.001 mol) of N-benzyloxycarbonyl alanine (Z-Ala), 0.08 g (0.001 mol) of pyridine and 0.256 g (0.001 mol) of DSC in 10 ml of acetonitrile was stirred at ambient temperature. After silica gel TLC. showed that Z-Ala (the free acid form) disappeared in the solution, the reaction solution was concentrated to a small volume, and the concentrated solution was admixed with ethyl acetate and then washed with aqueous 4% NaHCO3, with 1 N-HCl and finally with a saturated aqueous solution of sodium chloride to remove the liberated N-hydroxysuccinimide. The solution so treated was distilled to remove the ethyl acetate. The resultant solid residue was admixed with a solution of 0.165 g (0.001 mol) of phenylalanine (Phe-OH) and 0.101 g (0.001 mol) of triethylamine in 20 ml of a mixed solvent of acetonitrile and water (4:6 by volume). 24 Hours later, the reaction solution was concentrated to a small volume, and the concentrated solution was admixed with ethyl acetate, washed with aqueous 4% NaHCO3, with 1 N-HCl and with a saturated aqueous solution of sodium chloride, followed by drying over anhydrous sodium sulfate. The dried solution was then filtered and the filtrate was distilled, affording a colorless crystalline substance. Recrystallization of this crystalline substance from methylene chloride-ethyl ether gave 0.34 g of N-benzyloxycarbonylalanyl-phenylalanine (Z-Ala-Phe-OH) as a colorless crystalline substance. Yield 90%.

Workup

  1. concentrationthe reaction solution was concentrated to a small volume
  2. washwashed with aqueous 4% NaHCO3, with 1 N-HCl and finally with a saturated aqueous solution of sodium chloride
  3. customto remove the liberated N-hydroxysuccinimide
  4. additionThe solution so treated
  5. distillationwas distilled
  6. customto remove the ethyl acetate
  7. concentration24 Hours later, the reaction solution was concentrated to a small volume
  8. washwashed with aqueous 4% NaHCO3, with 1 N-HCl and with a saturated aqueous solution of sodium chloride
  9. dry with materialby drying over anhydrous sodium sulfate
  10. filtrationThe dried solution was then filtered
  11. distillationthe filtrate was distilled
  12. customaffording a colorless crystalline substance
  13. customRecrystallization of this crystalline substance from methylene chloride-ethyl ether

Sources & evidence

ORD record
ord-944bf4c53a2e44acb7e3834e81917bbb
Source dataset
uspto-grants-1982_07
Patent number
US04341707

Reaction notes

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