Cyclooctanone → Methyl 4-[cyclooctylidene(4-hydroxyphenyl)methyl]benzoate

HRID 2100138Notes

Reaction equation

HRID 2100138 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:11]=2)=O)=[CH:4][CH:3]=1.[C:20]1(=O)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1>C1COCC1.[Zn].Cl[Ti](Cl)(Cl)Cl>[C:20]1(=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=2)[C:10]2[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:11]=2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

6

Reactant 2

HCID 10403CyclooctanoneHCID 10038024Methyl 4-(4-hydroxybenzoyl)benzoate

Product 1

HCID 68654353Methyl 4-[cyclooctylidene(4-hydroxyphenyl)methyl]benzoateYield 60.2%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a 3-neck round-bottomed flask was added zinc powder (0.40 g, 6.12 mmoL) followed by anhydrous THF (15 mL). To the stirred suspension was slowly added TiCl4 (0.32 mL, 0.55 g, 2.9 mmoL) at RT under a nitrogen atmosphere. The reaction mixture was heated at reflux for 2 h. To the reaction mixture was added a solution of methyl 4-[(4-hydroxyphenyl)carbonyl]benzoate (24) (0.193 g, 0.75 mmoL) and cyclooctanone (0.31 g, 2.46 mmoL) in anhydrous THF (5 mL). The reaction mixture was heated at reflux under a nitrogen atmosphere to 2 h. The oil bath was removed and the reaction mixture was allowed to cool at RT. To the reaction mixture was added H2O (5 mL) followed by 10% K2CO3 (5 mL). The reaction mixture was filtered through a pad of Celite with the aid of H2O and EtOAc. The filtrate was transferred to a separatory funnel and the layers were separated. The organic phase was dried (MgSO4), filtered, and the filtrate was concentrated to give a yellow oil. The crude product was purified by flash chromatography on silica gel with a CH2Cl2:MeOH gradient (100:0 to 95:5) to give 0.159 g (60%) of compound 158 as an oil. 1H NMR (400 MHz, DMSO-d6): δ 1.36-1.54 (m, 8 H), 1.59 (m, 2 H), 2.14 (m, 2 H), 2.20 (m, 2 H), 3.80 (s, 3 H), 6.67 (d, J=8.3 Hz, 2 H), 6.93 (d, J=8.3 Hz, 2 H), 7.26 (d, J=8.1 Hz, 2 H), 7.87 (d, J=8.1 Hz, 2 H), 9.30 (s, 1 H).

Workup

  1. customat RT
  2. temperatureThe reaction mixture was heated
  3. temperatureat reflux for 2 h
  4. temperatureThe reaction mixture was heated
  5. temperatureat reflux under a nitrogen atmosphere to 2 h
  6. customThe oil bath was removed
  7. additionTo the reaction mixture was added H2O (5 mL)
  8. filtrationThe reaction mixture was filtered through a pad of Celite with the aid of H2O and EtOAc
  9. customThe filtrate was transferred to a separatory funnel
  10. customthe layers were separated
  11. dry with materialThe organic phase was dried (MgSO4)
  12. filtrationfiltered
  13. concentrationthe filtrate was concentrated
  14. customto give a yellow oil
  15. customThe crude product was purified by flash chromatography on silica gel with a CH2Cl2

Sources & evidence

ORD record
ord-5a590f50b78947fbacba72adb87b0497
Source dataset
uspto-grants-2009_08
Patent number
US07569601B2

Reaction notes

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