2-Bromo-3-methyl-2-cyclopenten-1-ol → 2-Ethyl-3-methyl-cyclopent-2-enol

HRID 9301

Reaction equation

HRID 9301 reaction equation
Br[C:2]1[CH:3]([OH:8])[CH2:4][CH2:5][C:6]=1[CH3:7].[CH2:9]([Mg]Br)[CH3:10]>C1COCC1.[Ni](Cl)Cl.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:9]([C:2]1[CH:3]([OH:8])[CH2:4][CH2:5][C:6]=1[CH3:7])[CH3:10]

Participants

5

Reactant 2

HCID 107497992-Bromo-3-methyl-2-cyclopenten-1-olHCID 178418443HCID 178418443, compound

Product 1

HCID 219861782-Ethyl-3-methyl-cyclopent-2-enol

Reagents, catalysts & solvents 2

HCID 2724937Dichloro(1,1'-(1,3-propanediyl)bis(1,1-diphenylphosphine-kappaP))nickelCatalystHCID 8028TetrahydrofuranSolvent

Procedure

The alcohol (Intermediate V2, 16 mmol) in THF (30 mL) at 0° C. was treated with ethyl magnesium bromide (40 mmol). The catalyst, 1,3-bis(diphenylphosphino)propane nickel (11) chloride (0.75 mmol) (NiCl2dppp) was added in one portion and the mixture was heated to reflux for 3 hours following the procedure of Organ et al. J. Org. Chem. 1997, 62, 1523, incorporated herein by reference.) The reaction mixture was cooled to rt and quenched with sat. NH4Cl solution. The mixture was filtered and partitioned between brine and diethyl ether. The organic layer was removed and dried over Na2SO4, filtered and concentrated under vacuum. The oil was purified by chromatography on SiO2 with 20% EtOAc:Hx to yield 2-ethyl-3-methyl-cyclopent-2-enol (Intermediate V3). Use of the alcohol (Intermediate V3) in the applicable steps of Method A and Method P produced 4-(2-ethyl-3-methyl-cyclopent-2-enylmethyl)-1,3-dihydro-imidazol-2-one (Compound 64). 1H NMR (300 MHz, CD3OD-d4): δ 6.03 (s, 1H), 2.88 (brs, 1H), 2.65–2.59 (m, 1H), 2.27–1.83 (series of m, 6H), 1.62 (s, 3H), 1.54–1.45 (m, 1H), 0.97 (t, J=6 Hz, 3H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 3 hours
  3. customquenched with sat. NH4Cl solution
  4. filtrationThe mixture was filtered
  5. custompartitioned between brine and diethyl ether
  6. customThe organic layer was removed
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customThe oil was purified by chromatography on SiO2 with 20% EtOAc

Sources & evidence

ORD record
ord-bfaeb299ce614cc1b00cd1c3898b5524
Source dataset
uspto-grants-2006_08
Patent number
US07091232B2

Linked notes

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