Triethylamine → N-benzyloxycarbonyl-L-prolyl-L-prolinal diethyl acetal

HRID 467155Notes

Reaction equation

HRID 467155 reaction equation
Cl.[CH2:2]([O:4][CH:5]([O:11][CH2:12][CH3:13])[C@@H:6]1[CH2:10][CH2:9][CH2:8][NH:7]1)[CH3:3].[CH2:14]([O:21][C:22]([N:24]1[CH2:31][CH2:30][CH2:29][C@H:25]1[C:26](O)=[O:27])=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>ClCCl.CCOCC>[CH2:12]([O:11][CH:5]([O:4][CH2:2][CH3:3])[C@@H:6]1[CH2:10][CH2:9][CH2:8][N:7]1[C:26](=[O:27])[C@@H:25]1[CH2:29][CH2:30][CH2:31][N:24]1[C:22]([O:21][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:23])[CH3:13]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 101987Benzyloxycarbonyl-L-prolineHCID 86746304L-prolinal diethyl acetal hydrochloride

Product 1

HCID 15132645N-benzyloxycarbonyl-L-prolyl-L-prolinal diethyl acetalYield 69%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of L-prolinal diethyl acetal hydrochloride (898 mg) and benzyloxycarbonyl-L-proline (1.2 g, 4.82 mmol) in dichloromethane (15 ml) are added successively, under ice-cooling and agitation, 1-hydroxy-benzotriazole (645 mg), triethylamine (0.68 ml, 4.88 mmol) and N,N-dicyclohexylcarbodiimide (1.0 g, 4.90 mmol). After the addition, stirring is further continued for 2 hours under ice-cooling, and then for 45 minutes at room temperature. Ether (40 ml) is added to the reaction mixture and the mixture is filtered for removal of insolubles. The filtrate is washed successively with water (10 ml), a saturated aqueous solution of sodium hydrogen carbonate (10 ml) and a saturated aqueous solution of edible salt (10 ml), dried over magnesium sulfate and filtered. The filtrate is concentrated to dryness under reduced pressure. The residue is purified by column chromatography on silica gel (benzene-ether-ethanol, 20:20:1) to give 1.125 g (69%) of the title compound as pale yellow crystals.

Workup

  1. temperaturecooling
  2. additionAfter the addition
  3. temperaturecooling
  4. waitfor 45 minutes at room temperature
  5. filtrationthe mixture is filtered for removal of insolubles
  6. washThe filtrate is washed successively with water (10 ml)
  7. dry with materiala saturated aqueous solution of sodium hydrogen carbonate (10 ml) and a saturated aqueous solution of edible salt (10 ml), dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate is concentrated to dryness under reduced pressure
  10. customThe residue is purified by column chromatography on silica gel (benzene-ether-ethanol, 20:20:1)

Sources & evidence

ORD record
ord-276b74bdd07a494a8df92473eae67a02
Source dataset
uspto-grants-1992_10
Patent number
US05158970

Reaction notes

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