Potassium Carbonate → HCID 11406882, compound

HRID 2100099Notes

Reaction equation

HRID 2100099 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][CH:11]=2)=O)=[CH:4][CH:3]=1.[CH3:20][C:21]1([CH3:30])[CH2:26][C:25]([CH3:28])([CH3:27])[CH2:24][C:23](=O)[CH2:22]1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.[Zn].Cl[Ti](Cl)(Cl)Cl>[CH3:19][S:16]([C:13]1[CH:14]=[CH:15][C:10]([C:8](=[C:23]2[CH2:24][C:25]([CH3:28])([CH3:27])[CH2:26][C:21]([CH3:30])([CH3:20])[CH2:22]2)[C:5]2[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=2)=[CH:11][CH:12]=1)(=[O:18])=[O:17]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 843993,3,5,5-TetramethylcyclohexanoneHCID 21701225HCID 21701225, compound

Product 1

HCID 11406882HCID 11406882, compoundYield 76.4%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred suspension of zinc powder (0.36 g, 5.50 mmol) in THF (15 mL) was slowly added TiCl4 (0.30 mL, 2.75 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-(methylsulfonyl)phenyl]methanone (93) (0.19 g, 0.69 mmol) and 3,3,5,5-tetramethyl cyclohexanone (0.33 g, 2.06 mmol) in THF (4 mL) was added to the mixture. The reaction mixture was heated at reflux with stirring under a nitrogen atmosphere for 1.5 h. The reaction mixture was allowed to cool at room temperature. To the reaction mixture was slowly added 10% aqueous K2CO3 (15 mL). The reaction mixture was filtered through a pad of celite and the pad washed with ethyl acetate (70 mL). The filtrate was transferred to a separatory funnel and the layers were separated. The aqueous layer was further extracted with ethyl acetate (25 mL). The combined organic phase 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 25% EtOAc:hexanes to give white foam residue, which was triturated with hot hexanes (containing 1% MeOH) to afford 0.21 g (76%) of the title compound (94) as white solid, m.p. 149-150° C. 1H NMR (300 MHz, DMSO-d6): δ 0.90 (s, 6H), 0.91 (s, 6H), 1.28 (s, 2H), 1.88 (s, 2H), 1.95 (s, 2H), 3.20 (s, 3H), 6.70 (d, J=8.4 Hz, 2H), 6.97 (d, J=8.4 Hz, 2H), 7.40 (d, J=8.2 Hz, 2H), 7.84 (d, J=8.2 Hz, 2H), 9.34 (s, 1H). LCMS (ES): m/z 397 (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 washed with ethyl acetate (70 mL)
  8. customThe filtrate was transferred to a separatory funnel
  9. customthe layers were separated
  10. extractionThe aqueous layer was further extracted with ethyl acetate (25 mL)
  11. washThe combined organic phase 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 25% EtOAc
  18. customhexanes to give white foam residue, which
  19. customwas triturated with hot hexanes (containing 1% MeOH)

Sources & evidence

ORD record
ord-057898c5f1fb4d3b88375bf24267a519
Source dataset
uspto-grants-2009_08
Patent number
US07569601B2

Reaction notes

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