4-Methylmorpholine → HCID 131722742, compound

HRID 1383726Notes

Reaction equation

HRID 1383726 reaction equation
CSC(SC)=[N:4][C@H:5]([C:17]([OH:19])=O)[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH:8]=1.C[N:23]1CCOCC1.ClC(OCC)=O>CN(C=O)C>[NH2:4][C@H:5]([C:17]([NH2:23])=[O:19])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH:8]=1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 86757100HCID 86757100, compound

Product 1

HCID 131722742HCID 131722742, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 492 mg (1.51 mmol) of N-[bis-(methyl-thio)methylene]-3-t-butylphenylalanine in 5 ml of DMF, 0.183 ml (1.66 mmol) of NMM and 0.159 ml (1.66 mmol) of ethyl chloroformate were added at −15° C. and the mixture was stirred for 30 minutes. The reaction mixture was stirred with bubbling of ammonia gas for another 30 minutes, left to stand at room temperature, diluted with ethyl acetate and washed first with water, then with saturated brine. The organic layer was dried with anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure; the resulting residue was dissolved in 3 ml of 1,4-dioxane and, after adding 1 ml of 2 N hydrochloric acid, the solution was stirred at room temperature for 3 days. Under cooling with ice, the solution was neutralized with saturated aqueous NaHCO3, extracted with chloroform, and washed first with water, then with saturated brine. The organic layer was dried with magnesium sulfate and concentrated under reduced pressure; the resulting residue was subjected to silica gel column chromatography (eluting solvent; chloroform:methanol=10:1) to give Phe(3-tBu)-NH2 in the amount of 210 mg (63%).

Workup

  1. stirringThe reaction mixture was stirred
  2. customwith bubbling of ammonia gas for another 30 minutes
  3. waitleft
  4. customto stand at room temperature
  5. additiondiluted with ethyl acetate
  6. washwashed first with water
  7. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. dissolutionthe resulting residue was dissolved in 3 ml of 1,4-dioxane
  10. additionafter adding 1 ml of 2 N hydrochloric acid
  11. stirringthe solution was stirred at room temperature for 3 days
  12. temperatureUnder cooling with ice
  13. extractionextracted with chloroform
  14. washwashed first with water
  15. dry with materialThe organic layer was dried with magnesium sulfate
  16. concentrationconcentrated under reduced pressure
  17. washthe resulting residue was subjected to silica gel column chromatography (eluting solvent; chloroform:methanol=10:1)

Sources & evidence

ORD record
ord-83317e49e1864bac90ed1fef3818e153
Source dataset
uspto-grants-2001_07
Patent number
US06255285B1

Reaction notes

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