Ethyl Acetate → HCID 18611251, compound

HRID 2413736Notes

Reaction equation

HRID 2413736 reaction equation
Cl.C([O:9][C:10](=[O:28])[C@@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16](=[O:27])[C@@H:17]1[CH2:21][CH2:20][CH2:19][N:18]1[C:22](=[O:26])[C@H:23]([CH3:25])[NH2:24])C1C=CC=CC=1.C([O:32][CH2:33][CH3:34])(=O)C>CN(C)C=O.C(N(CC)CC)C>[NH:18]1[C:22](=[O:26])[CH2:23][CH2:25][C@H:34]1[C:33]([NH:24][C@H:23]([C:22]([N:18]1[CH2:19][CH2:20][CH2:21][C@H:17]1[C:16]([N:12]1[CH2:13][CH2:14][CH2:15][C@H:11]1[C:10]([OH:9])=[O:28])=[O:27])=[O:26])[CH3:25])=[O:32]

Participants

5

Reactant 2

HCID 8857Ethyl AcetateHCID 22827652HCID 22827652, compound

Product 1

HCID 18611251HCID 18611251, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent2×

Procedure

L-alanyl-L-prolyl-L-proline benzylester hydrochloride (2.46 g, 6 m mole) was dissolved in dimethylformamide (10 ml, and triethylamine (0.84 ml, 6m mole) was added thereto under cooling to neutralize it and then benzyloxycarbonyl-L-pyroglutamic acid N-hydroxysuccinimide ester (2.38 g, 6.6 m mole) was added thereto. The mixture was stirred for 2 days while the solution had been adjusted to a pH of about 7 with triethylamine and then ethyl acetate (150 ml) was added thereto. The solution was washed with 1N hydrochloric acid, 5% aqueous sodium bicarbonate and water in order. The ethyl acetate layer was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. To the thus obtained residue, n-hexane was added to form a powder. This powder was purified by column chromatography. (Silica gel, developing solvent; chloroform:ethanol:ethyl acetate=5:1:5). The fractions of the main ingredient were collected together and then concentrated. To the residue, n-hexane was added to precipitate the powder. They were dissolved in methanol (50 ml) and then hydrogen gas passed through the solution in the presence of palladium-carbon as a catalyst for 4 hours. The catalyst was separated by filtration and the solvent was distilled off. The thus obtained residue was recrystallized with methanol-ether to give L-pyroglutamyl-L-alanyl-L-prolyl-L-proline (880 mg).

Workup

  1. additionwas added
  2. temperatureunder cooling
  3. washThe solution was washed with 1N hydrochloric acid, 5% aqueous sodium bicarbonate and water in order
  4. dry with materialThe ethyl acetate layer was dried over anhydrous sodium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. additionTo the thus obtained residue, n-hexane was added
  7. customto form a powder
  8. customThis powder was purified by column chromatography
  9. customThe fractions of the main ingredient were collected together
  10. concentrationconcentrated
  11. additionTo the residue, n-hexane was added
  12. customto precipitate the powder
  13. dissolutionThey were dissolved in methanol (50 ml)
  14. waithydrogen gas passed through the solution in the presence of palladium-carbon as a catalyst for 4 hours
  15. customThe catalyst was separated by filtration
  16. distillationthe solvent was distilled off
  17. customThe thus obtained residue was recrystallized with methanol-ether

Sources & evidence

ORD record
ord-637ad63c46b648bcbeabffd92fa731d8
Source dataset
uspto-grants-1988_01
Patent number
US04719200

Reaction notes

Loading…