Potassium Carbonate → N-{4-[(4-Methoxy-phenyl)-(3,3,5,5-tetramethyl-cyclohexylidene)-methyl]phenyl}-benzenesulfonamide

HRID 2100154Notes

Reaction equation

HRID 2100154 reaction equation
[CH3:1][C:2]1([CH3:11])[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5][C:4](=O)[CH2:3]1.[CH3:12][O:13][C:14]1[CH:37]=[CH:36][C:17]([C:18]([C:20]2[CH:25]=[CH:24][C:23]([NH:26][S:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)(=[O:29])=[O:28])=[CH:22][CH:21]=2)=O)=[CH:16][CH:15]=1.C([O-])([O-])=O.[K+].[K+]>O1CCCC1.O.[Ti](Cl)(Cl)(Cl)Cl.[Zn]>[CH3:12][O:13][C:14]1[CH:15]=[CH:16][C:17]([C:18](=[C:4]2[CH2:3][C:2]([CH3:11])([CH3:1])[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5]2)[C:20]2[CH:25]=[CH:24][C:23]([NH:26][S:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)(=[O:29])=[O:28])=[CH:22][CH:21]=2)=[CH:36][CH:37]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 843993,3,5,5-TetramethylcyclohexanoneHCID 68654389HCID 68654389, compound

Product 1

HCID 68654350N-{4-[(4-Methoxy-phenyl)-(3,3,5,5-tetramethyl-cyclohexylidene)-methyl]phenyl}-benzenesulfonamideYield 80.3%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Titanium tetrachloride (0.50 mL, 4.53 mmol) was slowly added to a slurry of zinc powder (0.61 g, 9.31 mmol) in dry tetrahydrofuran (10 mL). The reaction mixture was heated at reflux for 2.5 h. A solution of 3,3,5,5-tetramethyl-cyclohexanone (0.64 mL, 3.67 mmol) and N-[4-(4-methoxy-benzoyl)-phenyl]-benzenesulfonamide (182) (0.45 g, 1.22 mmol) in dry tetrahdyrofuran (10 mL) was added to the reaction mixture and heated at reflux for another 2 h. The reaction mixture was cooled to room temperature and diluted with water (10 mL) followed by 10% K2CO3 (10 mL). The reaction mixture was filtered through a pad of Celite and the pad washed with EtOAc. The filtrate was transferred to a separatory funnel and the layers were separated. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash chromatography on silica gel with a hexanes:EtOAc gradient (100:0 to 55:45) to give 0.48 g (80%) of compound 183 as a white powder. 1H NMR (400 MHz, DMSO-d6): δ 0.81 (s, 6 H), 0.84 (s, 6 H), 1.21 (s, 2 H), 1.75, (s, 2 H), 1.85 (s, 2 H), 3.68 (s, 3 H), 6.79 (d, J=8.6 Hz, 2 H), 6.95-6.98 (m, 6 H), 7.47-7.50 (m, 2 H), 7.55-7.58 (m, 1 H), 7.69 (d, J=7.3 Hz, 2 H), 10.17 (s, 1 H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 2.5 h
  3. temperatureheated
  4. temperatureat reflux for another 2 h
  5. filtrationThe reaction mixture was filtered through a pad of Celite
  6. washthe pad washed with EtOAc
  7. customThe filtrate was transferred to a separatory funnel
  8. customthe layers were separated
  9. extractionThe aqueous layer was extracted with EtOAc
  10. washthe combined organic layers were washed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe crude material was purified by flash chromatography on silica gel with a hexanes

Sources & evidence

ORD record
ord-1258014c8ad7479ca8acbc4adaacc57e
Source dataset
uspto-grants-2009_08
Patent number
US07569601B2

Reaction notes

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