Methyl Acrylate → 3-[2-(tert-Butoxycarbonylamino-methyl)-phenyl]-acrylic acid methyl ester

HRID 456476Notes

Reaction equation

HRID 456476 reaction equation
[C:1]([O:5][C:6](=[O:16])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1Br)([CH3:4])([CH3:3])[CH3:2].[C:17]([O:21][CH3:22])(=[O:20])[CH:18]=[CH2:19]>CN(C=O)C.CCOC(C)=O>[CH3:22][O:21][C:17](=[O:20])[CH:18]=[CH:19][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[CH2:8][NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:16]

Participants

5

Reactant 2

HCID 7294Methyl AcrylateHCID 70183002-Bromo-N-(tert-butoxycarbonyl)benzylamine

Product 1

HCID 692195883-[2-(tert-Butoxycarbonylamino-methyl)-phenyl]-acrylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To compound of Step A (161.0 g, 561.8 mmol) in DMF (800 mL) was added methyl acrylate (58.0 g, 674.2 mmol), TEA (170.5 g, 1685.4 mmol) and dichlorobis(triphenylphosphine) palladium(II) (7.9 g, 11.2 mmol). The mixture was heated at 80° C. for about 32 hours. The mixture was cooled, diluted with 1000 mL of EtOAc and washed with 10% aqueous sodium bisulfate. The aqueous portion was extracted three times with EtOAc and the combined organics were dried (Na2SO4) and concentrated to dryness. The residue was dissolved in a small amount of DCM and filtered through 7 inches of silica gel in a 2 L sintered glass funnel eluting with 25% EtOAc/hexanes. The eluent was concentrated to dryness and recrystallized from EtOAc/hexanes to afford about 116.9 g (71%) of Step B compound.

Workup

  1. temperatureThe mixture was cooled
  2. washwashed with 10% aqueous sodium bisulfate
  3. extractionThe aqueous portion was extracted three times with EtOAc
  4. dry with materialthe combined organics were dried (Na2SO4)
  5. concentrationconcentrated to dryness
  6. dissolutionThe residue was dissolved in a small amount of DCM
  7. filtrationfiltered through 7 inches of silica gel in a 2 L sintered glass funnel
  8. washeluting with 25% EtOAc/hexanes
  9. concentrationThe eluent was concentrated to dryness
  10. customrecrystallized from EtOAc/hexanes
  11. customto afford about 116.9 g (71%) of Step B compound

Sources & evidence

ORD record
ord-60bd59abb09545078e6eef6bcadc9285
Source dataset
uspto-grants-2007_03
Patent number
US07186715B2

Reaction notes

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