Hexamethylphosphoramide → 2-(4-Bromo-2-methylphenyl)-3-pyridin-3-ylpropanenitrile

Temperatur

-78 °C

To a solution (4-bromo-2-methylphenyl)acetonitrile (III.1; 1 eq.) in THF (0.18M) and hexamethylphosphoramide (HMPA; 3.3 eq.) at −78° C. was added lithium hexamethyldisilazide (LiHMDS; 1.9 eq.). The reaction mixture was stirred 30 min at −78° C. To the resulting solution was cannulated a suspension of 3-(bromomethyl)pyridine hydrobromide salt (0.8 eq.) in THF (0.1M). The final mixture was allowed to warm slowly to 0° C., stirred 2 h, warm to room temperature then stirred for an extra 2 h. The resulting mixture was poured in saturated aqueous NaHCO3 and finally extracted with EtOAc. The organic extract was washed with water, brine, dried over Na2SO4 filtered and concentrated. Purification by column chromatography on silica gel (Combi-Flash by ISCO), eluting with Hex/EtOAc (0 to 60% in 30 min) afforded the desired compound as a colorless oil.

1. temperatureto warm slowly to 0° C.
2. stirringstirred 2 h
3. temperaturewarm to room temperature
4. stirringthen stirred for an extra 2 h
5. extractionfinally extracted with EtOAc
6. extractionThe organic extract
7. washwas washed with water, brine
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customPurification by column chromatography on silica gel (Combi-Flash by ISCO)
12. washeluting with Hex/EtOAc (0 to 60% in 30 min)

ORD-Eintrag

ord-c546dba1529c417484ab727b356a7372

Quelldatensatz

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08334308B2