Cyclopentanone → 1-[4-(1-Hydroxycyclopentyl)phenyl]cyclopropanecarboxylic acid

HRID 504305Notes

Reaction equation

HRID 504305 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([OH:13])=[O:12])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C([Mg]CCCC)CCC.C([Li])CCC.[C:28]1(=[O:33])[CH2:32][CH2:31][CH2:30][CH2:29]1>CCCCCCC.C1COCC1>[OH:33][C:28]1([C:2]2[CH:7]=[CH:6][C:5]([C:8]3([C:11]([OH:13])=[O:12])[CH2:10][CH2:9]3)=[CH:4][CH:3]=2)[CH2:32][CH2:31][CH2:30][CH2:29]1

Participants

7

Reactant 4

HCID 8452CyclopentanoneHCID 162279661-(4-Bromophenyl)cyclopropane-1-carboxylic acidHCID 178418339ButyllithiumHCID 178448196HCID 178448196, compound

Product 1

HCID 666623161-[4-(1-Hydroxycyclopentyl)phenyl]cyclopropanecarboxylic acid

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8900HeptaneSolvent

Conditions

Temperature
-20 °C

Procedure

A solution of 1-(4-bromophenyl)cyclopropanecarboxylic acid (600.0 mg, 0.002489 mol) in tetrahydrofuran (20 mL, 0.2 mol) was cooled below −20 Celsius under N2 atmosphere, and 1.0 M of dibutylmagnesium in heptane (1.3 mL) was slowly added to the solution while maintaining the temperature below −20 Celsius. Then n-butyllithium (2.5 M in hexane, 1.1 mL) was slowly added to the slurry while maintaining the temperature below −20 Celsius with effective stirring. After the mixture was stirred at −20 Celsius for 1 hour, a solution of cyclopentanone (0.264 mL, 0.00299 mol) in THF (20.0 mL) was added to the mixture. Then after stirring at −20 Celsius for 1 hour, the reaction was quenched with ammonium chloride and the reaction mixture was extracted with ethyl acetate. The organic phase was washed with brine, then dried over Na2SO4, and then filtered. The filtrate was concentrated. The residue was flash chromatographed on silica gel column with 30% ethyl acetate in hexanes to afford the desired compound. MS (ESI): 229.1 (M−OH−), 269.1 (M+Na+).

Workup

  1. temperaturewhile maintaining the temperature below −20 Celsius
  2. temperaturewhile maintaining the temperature below −20 Celsius with effective stirring
  3. stirringThen after stirring at −20 Celsius for 1 hour
  4. customthe reaction was quenched with ammonium chloride
  5. extractionthe reaction mixture was extracted with ethyl acetate
  6. washThe organic phase was washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated
  10. customchromatographed on silica gel column with 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-619857f816084ed68b7f04539ec5e5e6
Source dataset
uspto-grants-2010_08
Patent number
US07776874B2

Reaction notes

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