Triethylamine → Tert-butyl 3-(3-amino-2-methylphenyl)propanoate

HRID 1476051Notes

Reaction equation

HRID 1476051 reaction equation
[C:1]([O:5][C:6](=[O:9])[CH:7]=[CH2:8])([CH3:4])([CH3:3])[CH3:2].Br[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-])=O)[C:12]=1[CH3:20].C(N(CC)CC)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[Cl-].[NH4+]>CN(C=O)C.C(O)C.[Pd].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:17][C:13]1[C:12]([CH3:20])=[C:11]([CH2:8][CH2:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:9])[CH:16]=[CH:15][CH:14]=1

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 15458tert-Butyl acrylateHCID 25517Ammonium ChlorideHCID 80271Tri-o-tolylphosphineHCID 1235372-Bromo-6-nitrotoluene

Product 1

HCID 58136633Tert-butyl 3-(3-amino-2-methylphenyl)propanoate

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
125 °C

Procedure

Under argon, 201 ml (1.39 mol) of tert-butyl-prop-2-enoate were added dropwise to a solution of 100 g (463 mmol) of 1-bromo-2-methyl-3-nitrobenzene, 322 ml (2.31 mol) of triethylamine, 28.18 g (92.58 mmol) of tri-2-tolylphosphine and 10.39 g (46.29 mmol) of palladium(II) acetate in 2 liters of DMF, and the mixture was then stirred at 125° C. for 36 h. After cooling to room temperature, the reaction mixture was stirred with saturated aqueous ammonium chloride solution and the organic phase was separated off. The aqueous phase was extracted three times with tert-butyl methyl ether, and the combined organic phases were washed with saturated sodium chloride solution and dried over sodium sulphate. After filtration, the solvent was removed to dryness under reduced pressure. The residue obtained was purified by flash chromatography on silica gel (mobile phase petroleum ether/ethyl acetate 9:1). This gave 89 g (338 mmol, 73% of theory) of the intermediate tert-butyl-(2E)-3-(2-methyl-3-nitrophenyl)prop-2-enoate as a colourless solid. 88 g (334 mmol) of this solid were dissolved in 2 liters of ethanol, 7 g of palladium on carbon (10%) were added at room temperature and the mixture was hydrogenated under atmospheric pressure for 18 h. After complete conversion, the reaction solution was filtered through kieselguhr and the filtrate obtained was concentrated under reduced pressure. This gave 61.3 g (260.5 mmol, 78% of theory) of the title compound as a colourless solid.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe organic phase was separated off
  3. extractionThe aqueous phase was extracted three times with tert-butyl methyl ether
  4. washthe combined organic phases were washed with saturated sodium chloride solution
  5. dry with materialdried over sodium sulphate
  6. filtrationAfter filtration
  7. customthe solvent was removed to dryness under reduced pressure
  8. customThe residue obtained
  9. customwas purified by flash chromatography on silica gel (mobile phase petroleum ether/ethyl acetate 9:1)
  10. waitthe mixture was hydrogenated under atmospheric pressure for 18 h
  11. filtrationAfter complete conversion, the reaction solution was filtered through kieselguhr
  12. customthe filtrate obtained
  13. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-790f75e2f24840bbafd3abd473901903
Source dataset
uspto-grants-2015_04
Patent number
US09018414B2

Reaction notes

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