4-Methylmorpholine → HCID 178454158, compound

HRID 1655755Notes

Reaction equation

HRID 1655755 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:17]([OH:19])=[O:18])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[C@@H:21]([CH2:32][C:33]1[NH:34][CH:35]=CN=1)[C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23].[CH3:38][N:39]1CCOCC1>C(Cl)Cl.CN(C)C1C=CN=CC=1.O>[CH2:25]([O:24][C:22](=[O:23])[C@@H:21]([O:18][C:17](=[O:19])[C@H:9]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:32][C:33]1[N:34]=[CH:35][NH:39][CH:38]=1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

7

Reactant 3

HCID 79724-MethylmorpholineHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 54247798HCID 54247798, compound

Product 1

HCID 178454158HCID 178454158, compoundYield 13%

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

1.99 g of N-t butoxycarbonyl-L-phenylalanine and 1.58 g of benzyl (S)-α-hydroxyimidazolepropionate were suspended in 25 ml of methylene chloride and stirred. After stirring at room temperature for 15 minutes, 305 mg of 4-dimethylaminopyridine were added and the reaction mixture was cooled to -15°. After the dropwise addition of 2 ml of N-methylmorpholine and a solution of 6.6 g of propanephosphoric acid anhydride in 5 ml of methylene chloride, the reaction mixture was stirred at -15° for an additional 2 hours and left to stand at -18° for 6 days. After the addition of a few drops of water, the reaction mixture was evaporated under reduced pressure and the oily residue was triturated for 2 hours with 100 ml of ethyl acetate and 25 ml of water. The organic phase was then washed in succession with aqueous sodium bicarbonate solution (5%) water and 1.5M citric acid. The colorless oil obtained after evaporation of the solvent under reduced pressure was chromatographed on silica gel using a 95:5 mixture of methylene chloride and methanol as the eluting agent, to obtain (S)-α-[[N-(t-butoxycarbonyl) 3-phenyl-L-alanyl] oxy]imidazole-4-propionic acid benzyl ester as a yellow oil in 13% yield, MS: 494 (M+H)+.

Workup

  1. stirringAfter stirring at room temperature for 15 minutes
  2. temperaturethe reaction mixture was cooled to -15°
  3. waitleft
  4. customthe reaction mixture was evaporated under reduced pressure
  5. customthe oily residue was triturated for 2 hours with 100 ml of ethyl acetate and 25 ml of water
  6. washThe organic phase was then washed in succession with aqueous sodium bicarbonate solution (5%) water and 1.5M citric acid
  7. customThe colorless oil obtained
  8. customafter evaporation of the solvent under reduced pressure
  9. customwas chromatographed on silica gel using
  10. additiona 95:5 mixture of methylene chloride and methanol as the eluting agent

Sources & evidence

ORD record
ord-dbc994fcab8447628c519e8aa395e4a5
Source dataset
uspto-grants-1993_10
Patent number
US05250517

Reaction notes

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