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

HRID 1722186Notes

Reaction equation

HRID 1722186 reaction equation
[C:1]1([CH2:11][CH:12]([CH2:16][C:17]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[O:18])[C:13](O)=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Cl.[NH2:26][C@H:27]([C:29]([NH:31][C@@H:32]([CH2:41][CH:42]([CH3:44])[CH3:43])[CH:33]([OH:40])[C:34]([O:36][CH:37]([CH3:39])[CH3:38])=[O:35])=[O:30])[CH3:28].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]([CH2:16][C:17]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[O:18])[C:13]([NH:26][C@H:27]([C:29]([NH:31][C@@H:32]([CH2:41][CH:42]([CH3:44])[CH3:43])[CH:33]([OH:40])[C:34]([O:36][CH:37]([CH3:38])[CH3:39])=[O:35])=[O:30])[CH3:28])=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 139139432-(1-Naphthylmethyl)-3-morpholinocarbonylpropionic acidHCID 14070611isopropyl (2RS, 3S)-3-(L-alanyl)amino-2-hydroxy-5-methylhexanoate hydrochloride

Product 1

HCID 14070613isopropyl (2RS, 3S)-3-{N-[2-(1-naphthylmethyl)-3-(morpholinocarbonyl)propionyl]-L-alanyl}amino-2-hydroxy-5-methylhexanoateYield 13.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 79 mg of 2-(1-naphthylmethyl)-3-morpholinocarbonylpropionic acid and 90 mg of isopropyl (2RS, 3S)-3-(L-alanyl)amino-2-hydroxy-5-methylhexanoate hydrochloride in 5ml of N,N-dimethylformamide were added 0.062 ml of diphenylphosphoryl azide and 0.110 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. 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 = 5/1 by volume: Rf2 =0.70) to obtain 19 mg of isopropyl (2RS, 3S)-3-{N-[2-(1-naphthylmethyl)-3-(morpholinocarbonyl)propionyl]-L-alanyl}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 = 5/1 by volume: Rf2 =0.70)

Sources & evidence

ORD record
ord-c1646baba26a4f1b920e503e09b97072
Source dataset
uspto-grants-1989_08
Patent number
US04853463

Reaction notes

Loading…