Alternative Synthesis of Bilastine

Abstract

A new and efficient synthesis of the non-sedating histamine H1 receptor antagonist Bilastine is reported. The new route employs a convergent strategy, with a longest linear sequence of five steps, giving slightly improved yields over the previous routes. The use of anhydrous metal-halogen exchange, hazardous ethylene oxide, and a tedious protection of the carboxylic acid function are all avoided.

Keywords:

• Bilastine
• convergent synthesis
• hydroboration-oxidation
• Stille coupling
• Suzuki coupling
• vinyl boronic anhydride
• vinyl stannane

Notes

^a According to ¹H NMR analysis.

^b Conditions directly switched to LiCl/DMF; DMF alone was not tested.

^a According to GC and TLC analysis.