Sodium hydride → 4-[4-(3-Benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-benzonitrile

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 0.82 g of 4-(3-benzyloxy-propyl)-5-chloromethyl-2-(4-trifluoromethyl-phenyl)-thiazole in 12 mL of DMF at 0° C. was added 0.1 g NaH 55%. The reaction mixture was stirred at 0° C. for 10 min then 2-0.264 g of fluoro-4-hydroxybenzonitrile was added at this temperature. The reaction mixture was stirred at 0° C. for 1 h30, allowed to warm up to room temperature and then stirred for 4 h at room temperature. The solvent was removed and the resulting residue was taken up into dichloromethane then water was added. After decantation and separation, the aqueous layer was extracted three times with dichloromethane. The combined organic layers were washed with water, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give 0.91 g of crude product as a yellow oil. Purification by column chromatography on silica gel (heptane 1/ether 1) gave 840 mg of 4-[4-(3-benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-benzonitrile as a white foam.

Provenance & Evidence