Reaction #9397

Reaction equation

alcohol

2-bromo-3-methyl-cyclopent-2-enol

ethyl magnesium bromide

→

2-ethyl-3-methyl-cyclopent-2-enol

Solvents

THF

Conditions

Workup

1. 1
   Temperaturethe mixture was heated
2. 2
   Temperatureto reflux for 3 hours
3. 3
   Otherquenched with sat. NH4Cl solution
4. 4
   FiltrationThe mixture was filtered
5. 5
   Otherpartitioned between brine and diethyl ether
6. 6
   OtherThe organic layer was removed
7. 7
   Dryingdried over Na2SO4
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated under vacuum
10. 10
    OtherThe oil was purified by chromatography on SiO2 with 20% EtOAc

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).

Source