4-Methylmorpholine → HCID 178454356, compound

HRID 2051590Notes

Reaction equation

HRID 2051590 reaction equation
C(CC(O)=O)C.[C:7]([N:14]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C@H:15]([C:22](O)=[O:23])[CH2:16][C:17]1[N:21]=[CH:20][NH:19][CH:18]=1)([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].C[N:33]1CCOCC1.ClC(OCC(C)C)=O.C(OC[C@@H](N)CC(C)C)C>C(OCC)(=O)C>[C:7]([N:14]([C:25]([O:27][C:28]([CH3:31])([CH3:29])[CH3:30])=[O:26])[C@H:15]([C:22]([NH2:33])=[O:23])[CH2:16][C:17]1[N:21]=[CH:20][NH:19][CH:18]=1)([O:9][C:10]([CH3:11])([CH3:13])[CH3:12])=[O:8]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 15745497HCID 15745497, compoundHCID 178454358HCID 178454358, compound

Product 1

HCID 178454356HCID 178454356, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

A mixture of Nα -Nim -bis-BOC-histidine ethyl acetate solvale (1.92 g, 5.0 mmol), 4-methylmorpholine (0.55 mL, 5.0 mmol) and isobutyl chloroformate (0.65 mL, 5.0 mmol) in ethyl acetate (50 mL) was stirred in an ice bath under N2 for 15 minutes. A solution of (S)-1-ethoxy-2-amino-4-methylpentane (0.73 g, 5.0 mmol) in ethyl acetate (2 mL) was then added and the reaction stirred at room temperature for 20 hours. After washing with 10% citric acid, brine, saturated NaHCO3 solution and brine, the ethyl acetate extract was dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was flash chromatographed over silica gel. Elution with a mixture of 2% methanol and 98% chloroform afforded pure BOC-protected histidineamide (0.90 g).

Workup

  1. stirringthe reaction stirred at room temperature for 20 hours
  2. washAfter washing with 10% citric acid, brine, saturated NaHCO3 solution and brine
  3. extractionthe ethyl acetate extract
  4. dry with materialwas dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customchromatographed over silica gel
  8. washElution
  9. additionwith a mixture of 2% methanol and 98% chloroform afforded pure BOC-protected histidineamide (0.90 g)

Sources & evidence

ORD record
ord-1ff0c6a80f154f1a8a86bfcd3dd296af
Source dataset
uspto-grants-1991_05
Patent number
US05019647

Reaction notes

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