Triethylamine → N-benzyloxycarbonyl-3-(1-naphthyl)-L-alanyl-3-(4-thiazolyl)-DL-alanine methyl ester

HRID 255626Notes

Reaction equation

HRID 255626 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:24](O)=[O:25])[CH2:13][C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.Cl.[CH3:29][O:30][C:31](=[O:40])[CH:32]([CH2:34][C:35]1[N:36]=[CH:37][S:38][CH:39]=1)[NH2:33].P(C#N)(=O)(OCC)OCC.C(N(CC)CC)C>O1CCCC1>[CH3:29][O:30][C:31](=[O:40])[CH:32]([CH2:34][C:35]1[N:36]=[CH:37][S:38][CH:39]=1)[NH:33][C:24](=[O:25])[C@H:12]([CH2:13][C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16][CH:15]=1)[NH:11][C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:10]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 7020250Z-1-Nal-OHHCID 217527263-(4-thiazolyl)-DL-alanine methyl ester dihydrochloride

Product 1

HCID 53931154N-benzyloxycarbonyl-3-(1-naphthyl)-L-alanyl-3-(4-thiazolyl)-DL-alanine methyl esterYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2.90 g (8.30 mmole) of N-benzyloxycarbonyl-3-(1-naphthyl)-L-alanine and 2.15 g (8.30 mmole) of 3-(4-thiazolyl)-DL-alanine methyl ester dihydrochloride were suspended in 30 ml of anhydrous tetrahydrofuran. Whilst ice cooling, 1.51 ml (9.95 mmole) of diethyl phosphorocyanidate and 3.82 ml (27.4 mmole) of triethylamine were added dropwise under a nitrogen gas stream, and the mixture was stirred overnight at room temperature. The reaction product was condensed by evaporation under reduced pressure. Ethyl acetate was added to the residue, and the mixture was washed with water and then dried over anhydrous magnesium sulfate. The dried product was condensed by evaporation under reduced pressure, and the residue was purified by silica gel column chromatography eluted with a 10:1 by volume mixture of chloroform and methanol, to yield 2.62 g (61%) of N-benzyloxycarbonyl-3-(1-naphthyl)-L-alanyl-3-(4-thiazolyl)-DL-alanine methyl ester.

Workup

  1. customcondensed
  2. customby evaporation under reduced pressure
  3. additionEthyl acetate was added to the residue
  4. washthe mixture was washed with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customcondensed
  7. customby evaporation under reduced pressure
  8. customthe residue was purified by silica gel column chromatography
  9. washeluted with a 10:1 by volume mixture of chloroform and methanol

Sources & evidence

ORD record
ord-9c3f5db1418c4f6784e64ad437444329
Source dataset
uspto-grants-1987_10
Patent number
US04698329

Reaction notes

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