4-Methylmorpholine → HCID 178454166, compound

HRID 2051592Notes

Reaction equation

HRID 2051592 reaction equation
C(CC(O)=O)C.[C:7]([N:14](C(OC(C)(C)C)=O)[C@H:15]([C:22]([OH:24])=O)[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.N[C@@H](CC(C)C)CSCC>C(OCC)(=O)C>[C:7]([NH:14][C@H:15]([C:22]([NH2:33])=[O:24])[CH2:16][C:17]1[N:21]=[CH:20][NH:19][CH:18]=1)([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 54234050HCID 54234050, compoundHCID 178454358HCID 178454358, compound

Product 1

HCID 178454166HCID 178454166, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

A mixture of NαNim -bis BOC-(S)-histidine ethyl acetate solvate (0.96 g, 2.50 mmol), 4 methyl-morpholine (0.28 mL, 2.50 mmol) and isobutyl chloroformate (0.33 mL, 2.50 mmol) in ethyl acetate (35 mL) is stirred in an ice bath under N2 for 15 minutes. A solution of (S)-2-amino-1-ethylthio-4-methyl pentane (0.40 g, 2.50 mmol) in ethyl acetate (2 mL) is then added and the reaction stirred at room temperature for 18 hours. After washing with 10% citric acid, brine, saturated NaHCO3 solution and brine, the ethyl acetate extract is dried (Na2SO4), filtered and concentrated under reduced pressure. The residue is flash chromatographed over silica gel. Elution with a mixture of 2% methanol- 98% chloroform affords pure BOC-protected histidineamide.

Workup

  1. stirringthe reaction stirred at room temperature for 18 hours
  2. washAfter washing with 10% citric acid, brine, saturated NaHCO3 solution and brine
  3. extractionthe ethyl acetate extract
  4. dry with materialis dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customchromatographed over silica gel
  8. washElution
  9. additionwith a mixture of 2% methanol- 98% chloroform
  10. customaffords pure BOC-protected histidineamide

Sources & evidence

ORD record
ord-ae6280ed18d54d29b9533559572c5f97
Source dataset
uspto-grants-1991_05
Patent number
US05019647

Reaction notes

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