Dimethylformamide → Ethyl (2E)-3-{4-[(3-fluoro-4-hydroxyphenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenyl}-2-propenoate

HRID 2100122Notes

Reaction equation

HRID 2100122 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])[CH2:20][C:19]([CH3:26])([CH3:25])[CH2:18]2)[C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[C:11]([F: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>[F:16][C:11]1[CH:10]=[C:9]([C:8](=[C:17]2[CH2:18][C:19]([CH3:26])([CH3:25])[CH2:20][C:21]([CH3:23])([CH3:24])[CH2:22]2)[C:5]2[CH:6]=[CH:7][C:2](/[CH:29]=[CH:28]/[C:27]([O:31][CH2:32][CH3:33])=[O:30])=[CH:3][CH:4]=2)[CH:14]=[CH:13][C:12]=1[OH:15]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 8821Ethyl AcrylateHCID 686542754-[(4-Bromophenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]-2-fluorophenol

Product 1

HCID 68979876Ethyl (2E)-3-{4-[(3-fluoro-4-hydroxyphenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenyl}-2-propenoateYield 68.1%

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)(3,3,5,5-tetramethyl cyclohexylidene)methyl]-2-fluorophenol (139) (0.33 g, 0.79 mmol), ethyl acrylate (0.87 mL, 7.90 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.056 g, 0.08 mmol), Et3N (0.55 mL, 3.95 mmol) and DMF (10 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 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 15% EtOAc:hexanes to give 0.235 g (68%) of compound 140 as a light yellow viscous oil. 1H NMR (400 MHz, CDCl3): δ 0.92 (s, 6H), 0.94 (s, 6H), 1.29 (s, 2H), 1.32 (t, J=7.1 Hz, 3H), 1.95 (s, 2H), 1.97 (s, 2H), 4.25 (q, J=7.1 Hz, 2H), 4.98 (d, J=4.2 Hz, 1H), 6.39 (d, J=16.0 Hz, 1H), 6.80-6.95 (m, 3H), 7.16 (d, J=8.1 Hz, 2H), 7.43 (d, J=8.1 Hz, 2H), 7.65 (d, J=16.1 Hz, 1H). LCMS (ES): m/z, 437 (M+H)+, 435 (M−H)−.

Workup

  1. customThe stirred reaction mixture
  2. temperatureto cool to room temperature
  3. customThe layers were separated
  4. washthe organic phase 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 15% EtOAc

Sources & evidence

ORD record
ord-d18a9970389c46d09d8eb4b594bd2688
Source dataset
uspto-grants-2009_08
Patent number
US07569601B2

Reaction notes

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