Potassium Carbonate → N-{4-[[4-(methyloxy)phenyl](3,3,5,5-tetramethylcyclohexylidene)methyl]phenyl}acetamide

HRID 1716019Notes

Reaction equation

HRID 1716019 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:20])[CH3:19])=[CH:13][CH:12]=2)=O)=[CH:5][CH:4]=1.[CH3:21][C:22]1([CH3:31])[CH2:27][C:26]([CH3:29])([CH3:28])[CH2:25][C:24](=O)[CH2:23]1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.[Zn].Cl[Ti](Cl)(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[C:24]2[CH2:25][C:26]([CH3:29])([CH3:28])[CH2:27][C:22]([CH3:31])([CH3:21])[CH2:23]2)[C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:20])[CH3:19])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 843993,3,5,5-TetramethylcyclohexanoneHCID 13499420N-[4-(4-Methoxybenzoyl)phenyl]acetamide

Product 1

HCID 68654481N-{4-[[4-(methyloxy)phenyl](3,3,5,5-tetramethylcyclohexylidene)methyl]phenyl}acetamideYield 93.2%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred suspension of zinc powder (0.39 g, 5.94 mmol) in THF (15 mL) was slowly added TiCl4 (0.33 mL, 2.97 mmol) via syringe at RT under a nitrogen atmosphere. The mixture was heated at reflux for 2 h. A solution of N-(4-{[4-(methyloxy)phenyl]carbonyl}phenyl)acetamide (56) (0.20 g, 0.74 mmol) and 3,3,5,5-tetramethylcyclohexanone (0.35 g, 2.23 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 h. The reaction mixture was allowed to cool to 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 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 water, brine, dried (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 40% EtOAc:hexanes to give 0.27 g (93%) of compound 57 as colorless viscous oil. 1H NMR (400 MHz, CDCl3): δ 0.91 (s, 6H), 0.92 (s, 6H), 1.27 (s, 2H), 1.96 (s, 2H), 1.97 (s, 2H), 2.16 (s, 3H), 3.78 (s, 3H), 6.80 (d, J=8.6 Hz, 2H), 7.06 (d, J=8.8 Hz, 2H), 7.10 (d, J=8.5 Hz, 2H), 7.39 (d, J=8.5 Hz, 2H). LCMS (ESI): m/z 392 (M+H)+, 390 (M−H)−.

Workup

  1. customat RT
  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 water, brine
  12. dry with materialdried (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 40% EtOAc

Sources & evidence

ORD record
ord-12e9998c059649a7b5bcccda58845344
Source dataset
uspto-grants-2010_09
Patent number
US07799828B2

Reaction notes

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