4-Methylmorpholine → N-(3-methyl-2(S)-(t-butoxycarbonylamino)but-1-yl)phenylalanylmethionine-methyl ester

HRID 1900631Notes

Reaction equation

HRID 1900631 reaction equation
CN1CCOCC1.C(N=C=NCCCN(C)C)C.[CH3:19][CH:20]([CH3:43])[C@H:21]([NH:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:22][NH:23][C@H:24]([C:32]([OH:34])=O)[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.Cl.[CH3:45][O:46][C:47](=[O:54])[C@H:48]([CH2:50][CH2:51][S:52][CH3:53])[NH2:49].O.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[CH3:45][O:46][C:47](=[O:54])[C@H:48]([CH2:50][CH2:51][S:52][CH3:53])[NH:49][C:32](=[O:34])[C@H:24]([CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[NH:23][CH2:22][C@@H:21]([NH:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH:20]([CH3:19])[CH3:43]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 11435579L-Methionine, methyl ester, hydrochlorideHCID 22846563N-(3-methyl-2(S)-(t-butoxycarbonylamino)but-1-yl)phenylalanine

Product 1

HCID 22867014N-(3-methyl-2(S)-(t-butoxycarbonylamino)but-1-yl)phenylalanylmethionine-methyl esterYield 79.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-Methyl morpholine (4.0 ml) and 1-ethyl-3-(3-dimethylaminopropyl) carbodimide (EDC) hydrochloride (0.96 g, 0.005 mole) were added to a solution of the product of Step B (1.76 g, 0.005 mole), methionine methyl ester hydrochloride (1.0 g, 0.005 mole) and 1-hydroxybenzotriazole hydrate (HOBT,0.677 g, 0.005 mole) in dimethylformamide (DMF, 30 ml) the reaction mixture was stirred at room temperature over the weekend, concentrated in vacuo and taken up in ice, water, and ethyl acetate. After addition of 10% aqueous citric acid, the ethyl acetate solution was separated, washed with water (2×), aqueous NaHCO3 and brine, and dried over sodium sulfate. Filtration and evaporation of the ethyl acetate solution gave a pale yellow residue, which was purified by column chromatography (silica gel) using 35% ethyl acetate-hexane. The title compound (1.97 g) was obtained as a white solid.

Workup

  1. concentrationconcentrated in vacuo
  2. additionAfter addition of 10% aqueous citric acid
  3. customthe ethyl acetate solution was separated
  4. washwashed with water (2×), aqueous NaHCO3 and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationFiltration and evaporation of the ethyl acetate solution
  7. customgave a pale yellow residue, which
  8. customwas purified by column chromatography (silica gel)

Sources & evidence

ORD record
ord-5b00b4f4b29647cda6736e1a12a62473
Source dataset
uspto-grants-1996_11
Patent number
US05576293

Reaction notes

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