3,3,5,5-Tetramethylcyclohexanone → HCID 11992475, compound

HRID 2241027Notes

Reaction equation

HRID 2241027 reaction equation
[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=O)=[CH:10][CH:9]=1.[CH3:22][C:23]1([CH3:32])[CH2:28][C:27]([CH3:30])([CH3:29])[CH2:26][C:25](=O)[CH2:24]1>C1COCC1.[Zn].Cl[Ti](Cl)(Cl)Cl>[C:16]1([C:14](=[C:25]2[CH2:26][C:27]([CH3:30])([CH3:29])[CH2:28][C:23]([CH3:32])([CH3:22])[CH2:24]2)[C:11]2[CH:12]=[CH:13][C:8]([O:7][CH2:6][CH2:5][O:4][CH2:3][CH2:2][OH:1])=[CH:9][CH:10]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 2

HCID 843993,3,5,5-TetramethylcyclohexanoneHCID 68500397HCID 68500397, compound

Product 1

HCID 11992475HCID 11992475, compound

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred suspension of Zn (0.59 g, 8.94 mmol) in THF (10 mL) was added TiCl4 (0.50 mL, 4.47 mmol) dropwise. The mixture was refluxed under nitrogen for 2.5 h. Cooled to room temperature, a solution of 7 (0.32 g, 1.12 mmol) and 3,3,5,5-tetramethylcyclohexanone (0.53 g, 3.35 mmol) in THF (15 mL) was added and the reaction mixture was refluxed for another 2.5 h. Cooled to room temperature, the reaction was quenched with 10% K2CO3 (40 mL). The quenched 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, the layers were separated, and the aqueous layer was extracted with EtOAc (50 mL). The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated to a pale yellow oil. The residue was further purified by chromatography on a silica gel column eluted with a gradient from hexanes to 45% EtOAc:hexanes to give 8 as a white solid. Crystallization from 10:1 hexanes:EtOAc yielded colorless needles (0.27 g, 59%). mp 116-117° C. 1H NMR (400 MHz, CD3OD): δ0.91 (s, 6H), 0.93 (s, 6H), 1.29 (s, 2H), 1.95 (s, 2H), 1.99 (s, 2H), 3.60-3.65 (m, 2H), 3.65-3.70 (m, 2H), 3.80-3.85 (m, 2H), 4.05-4.15 (m, 2H), 6.85 (d, J=8.6 Hz, 2H), 7.06 (d, J=8.6 Hz, 2H), 7.10-7.20 (m, 3H), 7.20-7.30 (m, 2H). LRMS (ESI): m/z 409 (M+H)+. Anal. Calcd for C27H36O3: C, 79.37; H, 8.88. Found: C, 79.23; H, 8.95.

Workup

  1. temperatureThe mixture was refluxed under nitrogen for 2.5 h
  2. temperaturethe reaction mixture was refluxed for another 2.5 h
  3. temperatureCooled to room temperature
  4. customthe reaction was quenched with 10% K2CO3 (40 mL)
  5. customThe quenched reaction mixture
  6. filtrationwas 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 extracted with EtOAc (50 mL)
  11. washThe combined organic extracts were washed with brine
  12. dry with materialdried (Na2SO4)
  13. concentrationconcentrated to a pale yellow oil
  14. customThe residue was further purified by chromatography on a silica gel column
  15. washeluted with a gradient from hexanes to 45% EtOAc

Sources & evidence

ORD record
ord-122852f73d3448419ec6d7dcd8d32cc6
Source dataset
uspto-grants-2010_05
Patent number
US07723393B2

Reaction notes

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