反应详情

温度

-78 °C

To a solution (2′-chloro-3-methylbiphenyl-4-yl)acetonitrile (1 eq.) from step 1 in THF (0.10M) at −78° C. was added hexamethylphosphoramide (HMPA; 4 eq.) then lithium hexamethyldisilazide (LiHMDS; 1.2 eq.). The reaction mixture was stirred 30 min at −78° C. To the resulting solution was cannulated over 10 min a solution of 1,3-dichloro-2-{2-[4-(iodomethyl)phenoxy]ethoxy}-5-methylbenzene (II.1; 1.05 eq.). The final mixture was allowed to warm slowly to 0° C., stiffed an extra 2 h, poured in saturated aqueous NH4Cl and finally extracted with EtOAc. The organic extract was washed with water, brine, dried over MgSO4 filtered and concentrated. Purification by column chromatography on silica gel (Combi-Flash by ISCO), eluting with Hex/EtOAc (10 to 20% in 30 min) afforded the desired compound as a colorless oil.

1. waitTo the resulting solution was cannulated over 10 min
2. temperatureto warm slowly to 0° C.
3. waitstiffed an extra 2 h
4. extractionfinally extracted with EtOAc
5. extractionThe organic extract
6. washwas washed with water, brine
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customPurification by column chromatography on silica gel (Combi-Flash by ISCO)
11. washeluting with Hex/EtOAc (10 to 20% in 30 min)