Methyl iodide → Methyl 2-(4-phenylbicyclo[2.2.2]oct-1-yl)propanoate

Temperatur

-78 °C

To a solution of diisopropylamine (0.9 mL, 6.39 mmol) in anhydrous THF (10 mL) cooled to −78° C. (CO2/acetone) was added nBuLi (2M solution in cyclohexane; 3.2 mL, 6.4 mmol) and the reaction mixture was allowed to stir at −78° C. for 5 mins. Methyl (4-phenylbicyclo[2.2.2]oct-1-yl)acetate (Intermediate 1(ii); 1.5 g, 5.81 mmol) in anhydrous THF (2 mL) was added and the mixture immediately became dark brown/black. It was allowed to stir for ˜30 mins at −78° C. then methyl iodide (0.4 mL, 6.39 mmol) was added and the reaction mixture was allowed to warm to ambient temperature over 4 hrs. Saturated aqueous ammonium chloride solution (50 mL) was added and the mixture extracted into EtOAc (2×150 mL), the organic extracts were combined, dried (MgSO4) and concentrated to leave crude product which was an inseparable mixture of the title compound and starting material which was taken directly through to the next stage without further characterisation.

1. stirringto stir for ˜30 mins at −78° C.
2. temperatureto warm to ambient temperature over 4 hrs
3. extractionthe mixture extracted into EtOAc (2×150 mL)
4. dry with materialdried (MgSO4)
5. concentrationconcentrated
6. customto leave crude product which

ORD-Eintrag

ord-e0e5e4430d8f481b97f9d45474f23ec1

Quelldatensatz

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08017603B2