2-Cyclopentene-1-ol → 3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentanone

HRID 2199476Notes

Reaction equation

HRID 2199476 reaction equation
[CH2:1]([C@@H:7]1[CH2:16][CH2:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12](I)[CH:13]=2)[CH2:8]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].C([O-])(=O)C.[K+].[CH:23]1([OH:28])[CH2:27][CH2:26][CH:25]=[CH:24]1>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[CH2:1]([C@@H:7]1[CH2:16][CH2:15][C:14]2[CH:13]=[C:12]([CH:25]3[CH2:26][CH2:27][C:23](=[O:28])[CH2:24]3)[CH:11]=[CH:10][C:9]=2[CH2:8]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]

Participants

7

Reactant 3

HCID 2201642-Cyclopentene-1-olHCID 517044Potassium AcetateHCID 86730043(R)-2-hexyl-6-iodo-1,2,3,4-tetrahydronaphthalene

Product 1

HCID 867300443-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentanoneYield 57.9%

Reagents, catalysts & solvents 3

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Nitrogen gas was bubbled through a mixture of (R)-2-hexyl-6-iodo-1,2,3,4-tetrahydronaphthalene (I-8D, 11.8 g, 34.5 mmol), tetrabutylammonium chloride (9.58 g, 34.5 mmol), potassium acetate (10.15 g, 103 mmol), palladium (II) acetate (0.774 g, 3.45 mmol), and anhydrous DMF (100 mL) for 3 min before cyclopent-2-enol (6.8 g, 81 mmol, prepared according to Larock, R. C. et al., Tetrahedron, 50(2):305-321 (1994)) was added. Nitrogen gas was bubbled through the solution for an additional 2 min. The mixture was stirred at 80° C. under nitrogen for 2.5 h and then concentrated to remove DMF. The residue was mixed with water (150 ml) and extracted with ethyl acetate (4×50 mL). The combined ethyl acetate solutions were washed with water (30 mL), dried over anhydrous sodium sulfate, filtered through a silica gel pad, and concentrated under reduced pressure. Flash chromatography purification (220 g silica gel column, gradient elution from 5 to 50% ethyl acetate in hexanes) afforded 3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentanone (5.96 g, 19.97 mmol) LC/MS M=299.

Workup

  1. additionwas added
  2. customNitrogen gas was bubbled through the solution for an additional 2 min
  3. concentrationconcentrated
  4. customto remove DMF
  5. additionThe residue was mixed with water (150 ml)
  6. extractionextracted with ethyl acetate (4×50 mL)
  7. washThe combined ethyl acetate solutions were washed with water (30 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered through a silica gel pad
  10. concentrationconcentrated under reduced pressure
  11. customFlash chromatography purification (220 g silica gel column, gradient elution from 5 to 50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-6b7232db16914baa9772f768ed35c714
Source dataset
uspto-grants-2016_06
Patent number
US09359286B2

Reaction notes

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