Methyl Acrylate → HCID 54071285, compound

HRID 2416699Notes

Reaction equation

HRID 2416699 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:20][C:21]1[CH:22]=[C:23]([O:28][CH3:29])[CH:24]=[CH:25][C:26]=1Br)[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:30]([O:34][CH3:35])(=[O:33])[CH:31]=[CH2:32].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]([CH2:20][C:21]1[CH:22]=[C:23]([O:28][CH3:29])[CH:24]=[CH:25][C:26]=1[CH:32]=[CH:31][C:30]([O:34][CH3:35])=[O:33])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 7294Methyl AcrylateHCID 80271Tri-o-tolylphosphine2×HCID 81531DiisopropylethylamineHCID 22632173HCID 22632173, compound

Product 1

HCID 54071285HCID 54071285, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 3-[N-(tert-butoxycarbonyl)-N-(4-trifluoromethylbenzyl)aminomethyl]-4-bromoanisole (37.08 g, 78 mmol), methyl acrylate (35 mL, 390 mmol), palladium acetate (0.88 g, 3.9 mmol), tri-o-tolylphosphine (2.38 g, 7.8 mol), and diisopropylethylamine (31 mL, 178 mmol) in acetonitrile (200 mL) was deoxygenated (3 evacuation/argon purge cycles), then was heated to reflux under argon (oil bath set at 80° C.). After 6 hr additional palladium acetate (0.88 g, 3.9 mmol) and tri-o-tolylphosphine ((2.38 g, 7.8 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 several hr, then was filtered to remove a yellow precipitate. Concentration of the filtrate left the title compound (34.52 g, 92%) as a thick yellow oil: TLC (silica, 20% EtOAc/hexanes) Rf 0.45; 1H NMR (400 MHz, CDCl3) δ 7.80 (br s, 1H), 7.57 (d, J=8.1 Hz, 2H), 7.53 (d, J=8.6 Hz, 1H), 7.29 (br s, 2H), 6.83 (dd, 1H), 6.72 (br s, 1H), 6.23 (d, J=15.7 Hz, 1H), 4.58 and 4.53 (2 br s, 2H), 4.46 and 4.37 (2 br s, 2H), 3.80 (s, 3H), 3.77 (s, 3H), 1.49 (s, 9H).

Workup

  1. custom(3 evacuation/argon purge cycles)
  2. temperaturewas heated
  3. temperatureunder reflux for an additional 18 h
  4. concentrationThe reaction was concentrated to dryness
  5. filtrationA gray-colored precipitate was filtered off
  6. washwashed with a small volume of 1:1 Et2O/petroleum ether (100 mL)
  7. concentrationThe orangish-red filtrate was concentrated
  8. custompurified by flash chromatography on silica gel (15% ethyl acetate/hexanes)
  9. waitto stand for several hr
  10. filtrationwas filtered
  11. customto remove a yellow precipitate
  12. waitConcentration of the filtrate left the title compound (34.52 g, 92%) as a thick yellow oil

Sources & evidence

ORD record
ord-148373256f9b4b6f900232b8184d07c0
Source dataset
uspto-grants-2004_11
Patent number
US06825188B2

Reaction notes

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