Triethylamine → methyl (2RS, 3S)-3-{N-[2-(1-naphthylmethyl)-3-(morpholinocarbonyl)propionyl]-L-leucyl}amino-2-hydroxy-5-methylhexanoate

HRID 1722187Notes

Reaction equation

HRID 1722187 reaction equation
[C:1]1([CH2:11][CH:12]([CH2:24][C:25]([N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)=[O:26])[C:13]([NH:15][C@H:16]([C:21]([OH:23])=O)[CH2:17][CH:18]([CH3:20])[CH3:19])=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Cl.[NH2:34][C@@H:35]([CH2:42][CH:43]([CH3:45])[CH3:44])[CH:36]([OH:41])[C:37]([O:39][CH3:40])=[O:38].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(CC)CC)C>CN(C)C=O>[C:1]1([CH2:11][CH:12]([CH2:24][C:25]([N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)=[O:26])[C:13]([NH:15][C@H:16]([C:21]([NH:34][C@@H:35]([CH2:42][CH:43]([CH3:45])[CH3:44])[CH:36]([OH:41])[C:37]([O:39][CH3:40])=[O:38])=[O:23])[CH2:17][CH:18]([CH3:20])[CH3:19])=[O:14])[C:10]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 13746619methyl (2RS, 3S)-3-amino-2-hydroxy-5-methylhexanoate hydrochlorideHCID 14673343N-[2-(1-naphthylmethyl)-3-(morpholinocarbonyl)propionyl]-L-leucine

Product 1

HCID 14070634methyl (2RS, 3S)-3-{N-[2-(1-naphthylmethyl)-3-(morpholinocarbonyl)propionyl]-L-leucyl}amino-2-hydroxy-5-methylhexanoateYield 38.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 83 mg of N-[2-(1-naphthylmethyl)-3-(morpholinocarbonyl)propionyl]-L-leucine and 40 mg of methyl (2RS, 3S)-3-amino-2-hydroxy-5-methylhexanoate hydrochloride in 3 ml of N,N-dimethylformamide were added 0.049 ml of diphenylphosphoryl azide and 0.058 ml of triethylamine under ice-cooling, and the mixture was stirred overnight. The reaction mixture was evaporated under reduced pressure, and to the residue was added a 5% aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate, and the ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by preparative silica gel thin layer chromatography (developing solvent: chloroform/methanol = 10/1 by volume: Rf = 0.43) to obtain 43 mg of methyl (2RS, 3S)-3-{N-[2-(1-naphthylmethyl)-3-(morpholinocarbonyl)propionyl]-L-leucyl}amino-2-hydroxy-5-methylhexanoate as a white powder.

Workup

  1. temperaturecooling
  2. customThe reaction mixture was evaporated under reduced pressure
  3. additionto the residue was added a 5% aqueous sodium bicarbonate solution
  4. extractionThe mixture was extracted with ethyl acetate
  5. washthe ethyl acetate layer was washed with water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customevaporated under reduced pressure
  8. customThe residue was purified by preparative silica gel thin layer chromatography (developing solvent: chloroform/methanol = 10/1 by volume: Rf = 0.43)

Sources & evidence

ORD record
ord-1302a9e5489a48e9a4dbff1a6c0dea02
Source dataset
uspto-grants-1989_08
Patent number
US04853463

Reaction notes

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