Potassium Carbonate → 4-[(4-Iodophenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenol

HRID 1716080Notes

Reaction equation

HRID 1716080 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([I:16])=[CH:12][CH:11]=2)=O)=[CH:4][CH:3]=1.[CH3:17][C:18]1([CH3:27])[CH2:23][C:22]([CH3:25])([CH3:24])[CH2:21][C:20](=O)[CH2:19]1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.[Zn].Cl[Ti](Cl)(Cl)Cl>[I:16][C:13]1[CH:14]=[CH:15][C:10]([C:8](=[C:20]2[CH2:21][C:22]([CH3:25])([CH3:24])[CH2:23][C:18]([CH3:27])([CH3:17])[CH2:19]2)[C:5]2[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=2)=[CH:11][CH:12]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 843993,3,5,5-TetramethylcyclohexanoneHCID 13453359(4-Hydroxyphenyl)(4-iodophenyl)methanone

Product 1

HCID 686545464-[(4-Iodophenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenolYield 55%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred suspension of zinc powder (2.20 g, 33.6 mmol) in THF (75 mL) was slowly added TiCl4 (1.85 mL, 16.8 mmol) via syringe at room temperature under a nitrogen atmosphere. The mixture was heated at reflux for 2 h. A solution of (4-hydroxyphenyl)(4-iodophenyl)methanone (143) (1.36 g, 4.20 mmol) and 3,3,5,5-tetramethylcyclohexanone (1.98 g, 12.6 mmol) in THF (20 mL) was added to the mixture. The reaction mixture was heated at reflux with stirring under a nitrogen atmosphere for 25 minutes. The reaction mixture was allowed to cool to room temperature. To the reaction mixture was slowly added 10% aqueous K2CO3 (75 mL). The reaction mixture was filtered through a pad of Celite and the pad was washed with EtOAc (200 mL). The filtrate was transferred to a separatory funnel and the layers were separated. The aqueous layer was further extracted with EtOAc (50 mL). The combined organic phase was washed with water, brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as yellow 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 a solid residue, which was triturated with hot hexanes to afford 1.03 g (55%) compound 144 as white solid. mp 148-149° C. 1H NMR (400 MHz, DMSO-d6): δ 0.86 (s, 6H), 0.87 (s, 6H), 1.23 (s, 2H), 1.85 (s, 2H), 1.89 (s, 2H), 6.65 (d, J=8.4 Hz, 2H), 6.85-6.95 (m, 4H), 7.61 (d, J=8.3 Hz, 2H), 9.29 (s, 1H). LCMS (ESI): m/z 445 (M−H)−.

Workup

  1. customat room temperature
  2. temperatureThe mixture was heated
  3. temperatureat reflux for 2 h
  4. temperatureThe reaction mixture was heated
  5. temperatureat reflux
  6. filtrationThe reaction mixture was filtered through a pad of Celite
  7. washthe pad was washed with EtOAc (200 mL)
  8. customThe filtrate was transferred to a separatory funnel
  9. customthe layers were separated
  10. extractionThe aqueous layer was further extracted with EtOAc (50 mL)
  11. washThe combined organic phase was washed with water, brine
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationthe filtrate was concentrated
  15. customto give the crude product as yellow oil
  16. customThe crude product was purified by chromatography on a silica gel column
  17. washeluted with a gradient from hexanes to 15% EtOAc
  18. customhexanes to give a solid residue, which
  19. customwas triturated with hot hexanes

Sources & evidence

ORD record
ord-aa996ff68eff4a8296b061b26e0a6985
Source dataset
uspto-grants-2010_09
Patent number
US07799828B2

Reaction notes

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