3,3,5,5-Tetramethylcyclohexanone → 4-[(4-Fluorophenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenol

HRID 2241028Notes

Reaction equation

HRID 2241028 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([OH: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>[Zn].Cl[Ti](Cl)(Cl)Cl.C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([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:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 843993,3,5,5-TetramethylcyclohexanoneHCID 1176664-Fluoro-4'-hydroxybenzophenone

Product 1

HCID 111635614-[(4-Fluorophenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenolYield 80.5%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

The coupling procedure described for 1 (example 1, step 1) was employed. A mixture of (4-fluorophenyl)(4-hydroxyphenyl)methanone (4.32 g, 20 mmol), 3,3,5,5-tetramethylcyclohexanone (9.26 g, 60 mmol), Zn (13 g, 200 mmol), TiCl4 (10.9 mL, 100 mmol), and THF (400 mL) was refluxed for 2.5 h. Standard work-up followed by purification afforded 5.450 g (80%) of the title product 9 as a white solid. 1H NMR (400 MHz, CDCl3): δ 7.15-7.11 (m, 2H), 7.04 (d, J=8.7 Hz, 2H), 7.00-6.94 (m, 1H), 6.76 (d, J=8.7 Hz, 2H), 4.68 (br s, 1H), 2.0 (s, 2H), 1.96 (s, 2H), 1.31 (s, 2H), 0.95 (s, 6H), 0.94 (s, 6H). LCMS (APCI): m/z 429 (M+H)+.

Workup

  1. temperaturewas refluxed for 2.5 h
  2. customStandard work-up followed by purification

Sources & evidence

ORD record
ord-5f5fade24c7745a598bf11b6c7105bfc
Source dataset
uspto-grants-2010_05
Patent number
US07723393B2

Reaction notes

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