Potassium Carbonate → HCID 68654427, compound

HRID 229216Notes

Reaction equation

HRID 229216 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[C:12]([Cl:17])[CH:11]=2)=O)=[CH:4][CH:3]=1.[CH3:18][C:19]1([CH3:28])[CH2:24][C:23](=O)[CH2:22][C:21]([CH3:27])([CH3:26])[O:20]1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.[Zn].Cl[Ti](Cl)(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:23]2[CH2:22][C:21]([CH3:27])([CH3:26])[O:20][C:19]([CH3:28])([CH3:18])[CH2:24]2)[C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[C:12]([Cl:17])[CH:11]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 118296912,2,6,6-Tetramethyloxan-4-oneHCID 19043772HCID 19043772, compound

Product 1

HCID 68654427HCID 68654427, compoundYield 96.3%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred suspension of zinc powder (0.59 g, 8.99 mmol) in THF (20 mL) was slowly added TiCl4 (0.50 mL, 4.50 mmol) via syringe at room temperature under a nitrogen atmosphere. The mixture was heated at reflux for 2 h. A solution of (4-bromophenyl)(3-chloro-4-hydroxyphenyl)methanone (105) (0.35 g, 1.12 mmol) and 2,2,6,6-tetramethyl tetrahydro-4H-pyran-4-one (0.54 g, 3.37 mmol) in THF (6 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 to room temperature. To the reaction mixture was slowly added 10% aqueous K2CO3 (20 mL). The reaction mixture was filtered through a pad of Celite and the pad was washed with EtOAc (100 mL). The filtrate was transferred to a separatory funnel and the layers were separated. The aqueous layer was further extracted with EtOAc (25 mL). The combined organic phase was washed with brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as yellow viscous 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 0.47 g (96%) of compound 130 as a yellow viscous oil. 1H NMR (400 MHz, CDCl3): δ 1.20 (s, 6H), 1.22 (s, 6H), 2.18 (s, 2H), 2.22 (s, 2H), 5.47 (s, 1H), 6.90-7.00 (m, 2H), 7.02 (d, J=8.4 Hz, 2H), 7.09 (d, J=1.6 Hz, 1H), 7.43 (d, J=8.3 Hz, 2H). LCMS (ESI), m/z 433 (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 (100 mL)
  8. customThe filtrate was transferred to a separatory funnel
  9. customthe layers were separated
  10. extractionThe aqueous layer was further extracted with EtOAc (25 mL)
  11. washThe combined organic phase was washed with brine
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationthe filtrate was concentrated
  15. customto give the crude product as yellow viscous oil
  16. customThe crude product was purified by chromatography on a silica gel column
  17. washeluted with a gradient from hexanes to 15% EtOAc

Sources & evidence

ORD record
ord-951a624fac624c90b096cbecdde3075e
Source dataset
uspto-grants-2009_07
Patent number
US07560589B2

Reaction notes

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