Dimethylformamide → Ethyl (2E)-3-{4-[(3-chloro-4-hydroxyphenyl)(2,2,6,6-tetramethyltetrahydro-4H-pyran-4-ylidene)methyl]phenyl}-2-propenoate

HRID 1716067Notes

Reaction equation

HRID 1716067 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:17]2[CH2:22][C:21]([CH3:24])([CH3:23])[O:20][C:19]([CH3:26])([CH3:25])[CH2:18]2)[C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[C:11]([Cl:16])[CH:10]=2)=[CH:4][CH:3]=1.[C:27]([O:31][CH2:32][CH3:33])(=[O:30])[CH:28]=[CH2:29].CCN(CC)CC.CN(C=O)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCOC(C)=O.O>[Cl:16][C:11]1[CH:10]=[C:9]([C:8](=[C:17]2[CH2:18][C:19]([CH3:26])([CH3:25])[O:20][C:21]([CH3:23])([CH3:24])[CH2:22]2)[C:5]2[CH:4]=[CH:3][C:2](/[CH:29]=[CH:28]/[C:27]([O:31][CH2:32][CH3:33])=[O:30])=[CH:7][CH:6]=2)[CH:14]=[CH:13][C:12]=1[OH:15]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 8821Ethyl AcrylateHCID 68654427HCID 68654427, compound

Product 1

HCID 68975585Ethyl (2E)-3-{4-[(3-chloro-4-hydroxyphenyl)(2,2,6,6-tetramethyltetrahydro-4H-pyran-4-ylidene)methyl]phenyl}-2-propenoateYield 65.1%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a round-bottomed flask were added 4-[(4-bromophenyl)(2,2,6,6-tetramethyltetrahydro-4H-pyran-4-ylidene)methyl]-2-chlorophenol (130) (0.47 g, 1.08 mmol), ethyl acrylate (1.20 mL, 10.8 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.076 g, 0.11 mmol), Et3N (0.75 mL, 5.39 mmol) and DMF (12 mL). The stirred reaction mixture was heated overnight at 100° C. under a nitrogen atmosphere. The reaction mixture was allowed to cool to room temperature and transferred to a separatory funnel with the aid of water and EtOAc (100 mL). The layers were separated and the organic phase was washed with water, brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give brown oil. The crude product was purified by chromatography on a silica gel column eluted with a gradient from hexanes to 20% EtOAc:hexanes to give 0.32 g (65%) of the title compound as a yellow viscous oil. 1H NMR (400 MHz, CDCl3): δ 1.21 (s, 6H), 1.23 (s, 6H), 1.33 (t, J=7.1 Hz, 3H), 2.22 (s, 2H), 2.23 (s, 2H), 4.26 (q, J=7.1 Hz, 2H), 5.47 (s, 1H), 6.41 (d, J=15.9 Hz, 1H), 6.90-7.00 (m, 2H), 7.11 (d, J=1.6 Hz, 1H), 7.17 (d, J=8.3 Hz, 2H), 7.46 (d, J=8.0 Hz, 2H), 7.66 (d, J=15.9 Hz, 1H). LCMS (ESI), m/z, 455 (M+H)+, 453 (M−H)−.

Workup

  1. customThe stirred reaction mixture
  2. temperatureto cool to room temperature
  3. customThe layers were separated
  4. washthe organic phase was washed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated
  8. customto give brown oil
  9. customThe crude product was purified by chromatography on a silica gel column
  10. washeluted with a gradient from hexanes to 20% EtOAc

Sources & evidence

ORD record
ord-00ad3757cc8447c5ac39f624ce22317e
Source dataset
uspto-grants-2010_09
Patent number
US07799828B2

Reaction notes

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