3,5-Difluorobenzyl bromide → 3-(3,5-Difluorophenyl)-2-[2'-(3-methoxypropyl)-3-methylbiphenyl-4-yl]propanenitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of [2′-(3-methoxypropyl)-3-methylbiphenyl-4-yl]acetonitrile (1.2 eq.) from step 1 in THF (0.02M) at −78° C. was added lithium hexamethyldisilazide (LiHMDS; 1.3 eq.). The reaction mixture was stirred 15 min at −78° C. To the resulting solution was cannulated a solution of 3,5-difluorobenzyl bromide (1 eq.) in THF (0.04M). The final mixture was allowed to warm slowly to room temperature and then stirred and extra 4 h. The resulting mixture was poured in saturated aqueous NH4Cl and extracted with EtOAc. The organic extract was dried over Na2SO4, filtered and concentrated. Purification by column chromatography on silica gel (Combi-Flash by ISCO), eluting with Hex/EtOAc (0 to 50% in 30 min) afforded the desired compound as a colorless oil.

Provenance & Evidence