Methyl Acrylate → HCID 53753364, compound

HRID 2416705Notes

Reaction equation

HRID 2416705 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:14][C:15]1[CH:16]=[C:17]([O:22][CH3:23])[CH:18]=[CH:19][C:20]=1Br)[CH2:9][C:10]([F:13])([F:12])[F:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:24]([O:28][CH3:29])(=[O:27])[CH:25]=[CH2:26].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(C(C)C)CC)(C)C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:8]([CH2:14][C:15]1[CH:16]=[C:17]([O:22][CH3:23])[CH:18]=[CH:19][C:20]=1[CH:26]=[CH:25][C:24]([O:28][CH3:29])=[O:27])[CH2:9][C:10]([F:13])([F:12])[F:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 7294Methyl AcrylateHCID 80271Tri-o-tolylphosphine2×HCID 81531DiisopropylethylamineHCID 10572920HCID 10572920, compound

Product 1

HCID 53753364HCID 53753364, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 6342AcetonitrileSolvent

Procedure

A solution of 3-[N-(tert-butoxycarbonyl)-N-(2,2,2-trifluoroethyl)aminomethyl]-4-bromoanisole (48.19 g, 121 mmol), methyl acrylate (55 mL, 605 mmol), palladium acetate (1.36 g, 6.1 mmol), tri-o-tolylphosphine (3.69 g, 12 mol), and diisopropylethylamine (49 mL, 278 mmol) in acetonitrile (200 mL) was deoxygenated (3×evacuation/argon purge cycles), then was heated to reflux under argon in oil bath set at 80° C. After 6 hr additional palladium acetate (1.36 g, 6.1 mmol) and tri-o-tolylphosphine (3.69 g, 12 mmol) were added and the reaction was stirred under reflux for an additional 18 h. The reaction was concentrated to dryness, and the residue was taken up in 1:1 Et2O/petroleum ether (300 mL) and allowed to stand for 4 h. A gray-colored precipitate was filtered off and washed with a small volume of 1:1 Et2O/petroleum ether(˜100 mL). The orangish-red filtrate was concentrated and purified by flash chromatography on silica gel (15% ethyl acetate/hexanes). The resulting residue was taken up in hexane, and the mixture was allowed to stand for 2 hr, then was filtered to remove a yellow precipitate. Concentration of the filtrate left the title compound (45.85 g, 94%) as a yellow oil: TLC (20% EtOAc/hexane) Rf 0.50; 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J=16 Hz, 1H), 7.57 (d, J=9 Hz, 1H), 6.86 (dd, 1H), 6.74 and 6.72 (2s, 1H), 6.26 (d, J=16 Hz, 1H), 4.74 and 4.70 (2s, 2H), 3.83 (s, 3H), 3.79 (s, 3H), 3.80 and 3.66 (2m, 2H), 1.51 and 1.45 (2s, 9H).

Workup

  1. custom(3×evacuation/argon purge cycles)
  2. temperaturewas heated
  3. temperatureto reflux under argon in oil bath
  4. customset at 80° C
  5. temperatureunder reflux for an additional 18 h
  6. concentrationThe reaction was concentrated to dryness
  7. filtrationA gray-colored precipitate was filtered off
  8. washwashed with a small volume of 1:1 Et2O/petroleum ether(˜100 mL)
  9. concentrationThe orangish-red filtrate was concentrated
  10. custompurified by flash chromatography on silica gel (15% ethyl acetate/hexanes)
  11. waitto stand for 2 hr
  12. filtrationwas filtered
  13. customto remove a yellow precipitate
  14. waitConcentration of the filtrate left the title compound (45.85 g, 94%) as a yellow oil

Sources & evidence

ORD record
ord-1cfc58b3ead44b6980e6315f5cd09b48
Source dataset
uspto-grants-2004_11
Patent number
US06825188B2

Reaction notes

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