HCID 67206109, compound → HCID 58288401, compound

HRID 1476106Notes

Reaction equation

HRID 1476106 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:9]([CH2:15][CH2:16][CH3:17])=[CH:10][C:11]([O:13][CH3:14])=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8].NC1C=C(C(=CCC)CC(OC)=O)C=CC=1Cl>C(OCC)(=O)C.[Pd]>[NH2:1][C:2]1[CH:3]=[C:4]([CH:9]([CH2:15][CH2:16][CH3:17])[CH2:10][C:11]([O:13][CH3:14])=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 2

HCID 67206109HCID 67206109, compoundHCID 67207275HCID 67207275, compound

Product 1

HCID 58288401HCID 58288401, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

7.70 g (30.3 mmol) of the mixture of methyl 3-(3-amino-4-chlorophenyl)hex-2-enoate and methyl 3-(3-amino-4-chlorophenyl)hex-3-enoate (about 1.5:1, Example 164A) were dissolved in 45 ml of ethyl acetate, 646 mg (0.303 mmol) of palladium on carbon (5%) were added and the mixture was stirred under an atmosphere of hydrogen at atmospheric pressure and RT. After 10 h, the reaction mixture was filtered off through celite, the residue was washed with ethyl acetate and the filtrate was concentrated. The residue was taken up in about 50 ml of ethyl acetate, another about 650 mg of palladium on carbon (5%) were added and the mixture was stirred under an atmosphere of hydrogen at atmospheric pressure and RT. After a further 36 h, the reaction mixture was once more filtered off through celite, the residue was washed with ethyl acetate and the filtrate was concentrated. The residue was taken up in 800 ml of ethyl acetate, once more about 650 mg of palladium on carbon (5%) were added and the mixture was stirred under an atmosphere of hydrogen at atmospheric pressure and RT for 24 h. Again, the reaction mixture was filtered off through celite, the residue was washed with ethyl acetate and the filtrate was concentrated. The residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 50:1 to 10:1). This gave a total of 4.79 g of a mixture of target product and starting material. This mixture was dissolved in 180 ml of ethyl acetate, another 603 mg (0.566 mmol) of palladium on carbon (10%) were added and the mixture was stirred under an atmosphere of hydrogen at atmospheric pressure and RT overnight. The reaction mixture was filtered off through celite, the residue was washed with ethyl acetate, the filtrate was concentrated and the residue was dried under high vacuum. This gave 4.45 g (about 57% of theory) of the target product.

Workup

  1. filtrationthe reaction mixture was filtered off through celite
  2. washthe residue was washed with ethyl acetate
  3. concentrationthe filtrate was concentrated
  4. additionanother about 650 mg of palladium on carbon (5%) were added
  5. stirringthe mixture was stirred under an atmosphere of hydrogen at atmospheric pressure and RT
  6. waitAfter a further 36 h
  7. filtrationthe reaction mixture was once more filtered off through celite
  8. washthe residue was washed with ethyl acetate
  9. concentrationthe filtrate was concentrated
  10. additiononce more about 650 mg of palladium on carbon (5%) were added
  11. stirringthe mixture was stirred under an atmosphere of hydrogen at atmospheric pressure and RT for 24 h
  12. filtrationAgain, the reaction mixture was filtered off through celite
  13. washthe residue was washed with ethyl acetate
  14. concentrationthe filtrate was concentrated
  15. customThe residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 50:1 to 10:1)

Sources & evidence

ORD record
ord-d5ce8606d50f4255926f2ff43a6ac724
Source dataset
uspto-grants-2015_04
Patent number
US09018414B2

Reaction notes

Loading…