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

HRID 1476117Notes

Reaction equation

HRID 1476117 reaction equation
[C:1]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])(=[O:4])[CH:2]=[CH2:3].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-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:17][C:13]1[C:12]([CH3:20])=[C:11]([CH2:3][CH2:2][C:1]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4])[CH:16]=[CH:15][CH:14]=1

Participants

8

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 2

HCID 167845palladium(II) acetateCatalystHCID 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.

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)

Sources & evidence

ORD record
ord-147318a2633946ddbcd6819f41a76e84
Source dataset
uspto-grants-2015_04
Patent number
US09018414B2

Reaction notes

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