Methane → HCID 70058970, compound

HRID 2230293Notes

Reaction equation

HRID 2230293 reaction equation
[CH2:1]([O:8][C:9](=[O:19])[C@H:10]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[NH2:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=C(Cl)[O:22][C:23](Cl)(Cl)Cl.[CH4:28]>C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9](=[O:19])[C@@H:10]([NH:11][C:23]([N:11]1[CH2:10][CH2:12][CH2:13][CH2:14][CH2:15][CH2:28]1)=[O:22])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 297MethaneHCID 10426DiphosgeneHCID 736312Benzyl 3-phenyl-L-alaninate

Product 1

HCID 70058970HCID 70058970, compoundYield 166.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of phenylalanine benzyl ester (8.80 g, 23.4 mmol) in toluene was treated with diphosgene (4.63 g, 23.4 mmol) and activated charcoal (100 mg). The resulting suspension was heated at reflux for 4.5 hours then cooled to room temperature and stirred overnight. The reaction mixture was filtered through celite and concentrated. The residue was dissolved in EtOAc, cooled to 0° C. and treated with hexamethyleneimine (2.32 g, 23.4 mmol) and stirred for 2 hours. Additional hexamethyleneimine (1.0 mL) was added and the reaction mixture warmed to room temperature and stirred overnight. The reaction mixture was washed with 1N HCl solution, brine, dried (MgSO4) and concentrated. The residue was purified by chromatography (silica gel, gradient elution 4:1 hexane/EtOAc to 1:1 hexane/EtOAc) to give the title compound as a white solid (3.94 g, 44%).

Workup

  1. temperatureThe resulting suspension was heated
  2. temperatureat reflux for 4.5 hours
  3. filtrationThe reaction mixture was filtered through celite
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in EtOAc
  6. temperaturecooled to 0° C.
  7. stirringstirred for 2 hours
  8. temperaturethe reaction mixture warmed to room temperature
  9. stirringstirred overnight
  10. washThe reaction mixture was washed with 1N HCl solution, brine
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated
  13. customThe residue was purified by chromatography (silica gel, gradient elution 4:1 hexane/EtOAc to 1:1 hexane/EtOAc)

Sources & evidence

ORD record
ord-499012375f9f4b818900a728e2891438
Source dataset
uspto-grants-2002_07
Patent number
US06423689B1

Reaction notes

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