Water → 4-[(4,4-Dimethylcyclohexylidene)-(4-hydroxy-phenyl)-methyl]-benzoic acid methyl ester

HRID 229246Notes

Reaction equation

HRID 229246 reaction equation
[CH3:1][C:2]1([CH3:9])[CH2:7][CH2:6][C:5](=O)[CH2:4][CH2:3]1.[OH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([C:19]2[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][CH:20]=2)=O)=[CH:13][CH:12]=1.O.C([O-])([O-])=O.[K+].[K+]>O1CCCC1.[Zn].[Ti](Cl)(Cl)(Cl)Cl>[CH3:26][O:25][C:23](=[O:24])[C:22]1[CH:27]=[CH:28][C:19]([C:17](=[C:5]2[CH2:6][CH2:7][C:2]([CH3:9])([CH3:1])[CH2:3][CH2:4]2)[C:14]2[CH:15]=[CH:16][C:11]([OH:10])=[CH:12][CH:13]=2)=[CH:20][CH:21]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 138166Cyclohexanone, 4,4-dimethyl-HCID 10038024Methyl 4-(4-hydroxybenzoyl)benzoate

Product 1

HCID 686544214-[(4,4-Dimethylcyclohexylidene)-(4-hydroxy-phenyl)-methyl]-benzoic acid methyl esterYield 88%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a slurry of zinc powder (0.26 g, 4.01 mmol) in dry tetrahydrofuran (9 mL) was slowly added titanium tetrachloride (0.21 mL, 1.95 mmol). The reaction mixture was heated at reflux for 2.5 h, then a solution of 4,4-dimethyl-cyclohexanone (0.2 g, 1.58 mmol) and 4-(4-hydroxy-benzoyl)-benzoic acid methyl ester (24) (0.135 g, 0.53 mmol) in dry tetrahydrofuran (9 mL) was added. The reaction mixture was heated at reflux for 2 h. The reaction mixture was cooled to room temperature, water (5 mL) was added followed by 10% K2CO3 (5 mL). The reaction mixture was filtered through a pad of Celite and the pad was 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 loaded onto silica and purified by flash chromatography with a hexanes:EtOAc gradient (100:0 to 80:20) to give 0.162 g (88%) of the title compound 171 as an oil. 1H NMR (400 MHz, DMSO-d6): δ 0.93 (s, 6H), 1.31-1.33 (m, 4H), 2.12-2.19 (m, 4H), 3.81 (s, 3H), 6.66 (d, J=8.4 Hz, 2H), 6.84 (d, J=8.6 Hz, 2H), 7.18 (d, J=8.3 Hz, 2H), 7.86 (d, J=8.3 Hz, 2H), 9.36 (s, 1H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 2.5 h
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux for 2 h
  5. filtrationThe reaction mixture was filtered through a pad of Celite
  6. washthe pad was 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. custompurified by flash chromatography with a hexanes

Sources & evidence

ORD record
ord-7e417e3aea9b46a699ffe343378f8717
Source dataset
uspto-grants-2009_07
Patent number
US07560589B2

Reaction notes

Loading…