Hydrochloric Acid → 1-(Cyclopent-1-en-1-yl)-2,4-difluorobenzene

HRID 451096Notes

Reaction equation

HRID 451096 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[Mg]Br.[C:11]1(=O)[CH2:15][CH2:14][CH2:13][CH2:12]1.Cl>C1COCC1>[C:11]1([C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])[CH2:15][CH2:14][CH2:13][CH:12]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8452CyclopentanoneHCID 178505836HCID 178505836, compound

Product 1

HCID 580757581-(Cyclopent-1-en-1-yl)-2,4-difluorobenzeneYield 26.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 0.497M solution of (2,4-difluorophenyl)magnesium bromide (32.4 g, 149 mmol) in THF at 0° C. was carefully added cyclopentanone (13.23 mL, 149 mmol). Upon the end of the addition, the reaction mixture was heated at reflux for 2 h. Ice (10 g) and 6N aqueous hydrochloric acid were added. The reaction mixture was extracted with ether. The combined organic extracts were washed with a saturated aqueous solution of sodium hydrogen sulfite, a saturated aqueous solution of sodium bicarbonate and water. The organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuum and the residue was purified by column chromatography on silica gel to give 1-cyclopentenyl-2,4-difluorobenzene (7.064 g, 39.2 mmol, 26.3% yield) as colorless oil. LC-MS (M+H)+=181.0. 1H NMR (500 MHz, CDCl3) δ ppm 7.22-7.31 (1H, m), 6.75-6.85 (2H, m), 6.26-6.31 (1H, m), 2.68-2.74 (2H, m), 2.51-2.58 (2H, m), 1.93-2.02 (2H, m).

Workup

  1. customat 0° C.
  2. additionUpon the end of the addition
  3. temperaturethe reaction mixture was heated
  4. temperatureat reflux for 2 h
  5. extractionThe reaction mixture was extracted with ether
  6. washThe combined organic extracts were washed with a saturated aqueous solution of sodium hydrogen sulfite
  7. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. customThe solvent was removed in vacuum
  10. customthe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-24205c9f0b674f4ea7e39b344a73ec59
Source dataset
uspto-grants-2013_07
Patent number
US08486952B2

Reaction notes

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