(+/-)-Tert-butyl 3-[3-(benzylamino)-4-chlorophenyl]-2-cyclobutylpropanoate → (+/-)-Tert-butyl 3-(3-amino-4-chlorophenyl)-2-cyclobutylpropanoate

HRID 1476104Notes

Reaction equation

HRID 1476104 reaction equation
C([NH:8][C:9]1[CH:10]=[C:11]([CH2:16][CH:17]([CH:25]2[CH2:28][CH2:27][CH2:26]2)[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:12]=[CH:13][C:14]=1[Cl:15])C1C=CC=CC=1>C(OCC)(=O)C.[Pd]>[NH2:8][C:9]1[CH:10]=[C:11]([CH2:16][CH:17]([CH:25]2[CH2:26][CH2:27][CH2:28]2)[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:12]=[CH:13][C:14]=1[Cl:15]

Participants

4

Reactant 1

HCID 58288306(+/-)-Tert-butyl 3-[3-(benzylamino)-4-chlorophenyl]-2-cyclobutylpropanoate

Product 1

HCID 58288225(+/-)-Tert-butyl 3-(3-amino-4-chlorophenyl)-2-cyclobutylpropanoateYield 78.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 8857Ethyl AcetateSolvent

Procedure

1.85 g (4.63 mmol) of (+/−)-tert-butyl 3-[3-(benzylamino)-4-chlorophenyl]-2-cyclobutylpropanoate were dissolved in 10 ml of ethyl acetate and deoxygenated with argon, and 98 mg (0.093 mmol) of palladium on carbon (10%) were added. The reaction mixture was stirred at RT under an atmosphere of hydrogen at atmospheric pressure for 4 h and then allowed to stand over the weekend. The mixture was filtered through celite, the residue was washed with ethyl acetate, the filtrate was concentrated under reduced pressure and the residue of the filtrate was dried under high vacuum. This residue (about 1:1 mixture of starting material and target product) was once more dissolved in about 10 ml of ethyl acetate and deoxygenated with argon, and once more 98 mg (0.093 mmol) of palladium on carbon (10%) were added. Again, the reaction mixture was stirred at RT under an atmosphere of hydrogen at atmospheric pressure for 4 h. The mixture was then filtered through celite, the residue was washed with ethyl acetate, the filtrate was concentrated under reduced pressure and the residue was dried under high vacuum. Chromatographic purification on silica gel (mobile phase cyclohexane/ethyl acetate 20:1) gave 1.12 g of the target product (78.2% of theory).

Workup

  1. additionwere added
  2. filtrationThe mixture was filtered through celite
  3. washthe residue was washed with ethyl acetate
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customthe residue of the filtrate was dried under high vacuum
  6. additionThis residue (about 1:1 mixture of starting material and target product)
  7. dissolutionwas once more dissolved in about 10 ml of ethyl acetate
  8. additionwere added
  9. stirringAgain, the reaction mixture was stirred at RT under an atmosphere of hydrogen at atmospheric pressure for 4 h
  10. filtrationThe mixture was then filtered through celite
  11. washthe residue was washed with ethyl acetate
  12. concentrationthe filtrate was concentrated under reduced pressure
  13. customthe residue was dried under high vacuum
  14. customChromatographic purification on silica gel (mobile phase cyclohexane/ethyl acetate 20:1)

Sources & evidence

ORD record
ord-4438904d858642f0be69362f7fc745f1
Source dataset
uspto-grants-2015_04
Patent number
US09018414B2

Reaction notes

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