Pyridine → 2768-53-8

HRID 1759504Notes

Reaction equation

HRID 1759504 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>CN(C)C=O.C(OCC)(=O)C>[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 86.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of 0.223 g (0.001 mol) of N-benzyloxycarbonylalanine (Z-Ala), 0.08 g (0.001 mol) of pyridine and 0.256 g (0.001 mol) of DSC in 10 ml of dimethylformamide (DMF) 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 admixed with ethyl acetate and washed with aqueous 4% NaHCO3, with 1 N-HCl and with a saturated aqueous solution of sodium chloride. The solution so treated was then distilled to remove the ethyl acetate, leaving a solid residue. This 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 DMF, and the admixture so obtained was stirred at ambient temperature for 24 hours. Subsequently, the resultant reaction mixture was admixed with ethyl acetate, washed with aqueous 4% NaHCO3, with 1 N-HCl and with a saturated aqueous solution of sodium chloride to remove the liberated N-hydroxysuccinimide, followed by drying over anhydrous sodium sulfate. The dried solution was filtered and the filtrate was distilled to remove the solvent, affording a colorless crystalline substance. Recrystallization of this crystalline substance from methylene chloride-ethyl ether gave 0.321 g of N-benzyloxycarbonylalanyl-phenylalanine (Z-Ala-Phe-OH) as a colorless crystalline substance. Yield 86%.

Workup

  1. washwashed with aqueous 4% NaHCO3, with 1 N-HCl and with a saturated aqueous solution of sodium chloride
  2. additionThe solution so treated
  3. distillationwas then distilled
  4. customto remove the ethyl acetate
  5. customleaving a solid residue
  6. customthe admixture so obtained
  7. customSubsequently, the resultant reaction mixture
  8. washwashed with aqueous 4% NaHCO3, with 1 N-HCl and with a saturated aqueous solution of sodium chloride
  9. customto remove the liberated N-hydroxysuccinimide
  10. dry with materialby drying over anhydrous sodium sulfate
  11. filtrationThe dried solution was filtered
  12. distillationthe filtrate was distilled
  13. customto remove the solvent
  14. customaffording a colorless crystalline substance
  15. customRecrystallization of this crystalline substance from methylene chloride-ethyl ether

Sources & evidence

ORD record
ord-edc1af37aa844414843df7670e2f1696
Source dataset
uspto-grants-1982_07
Patent number
US04341707

Reaction notes

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