NEW ROUTE OF SYNTHESIS OF THE ANTIMALARIAL DRUG BENFLUMETOL

AIM：A new route of synthesis of benflumetol（I） by 5-step reactions was developed. METHODS: The starting material， fluorene（II）, was chlorinated with chlorine to yield 2,7-dichlorofluorene（III）， which underwent Friedel-Crafts acylation with chloroacetyl chloride to give 2,7-dichloro-4-chloroacetyl-fluorene（IV）. IV was reduced by means of KBH4 to provide 2,7-dichlorofluorenyl-4-ethylene oxide（V） which was then condensed with dibutylamine to yield α-（dibutylaminomethyl）-2,7-dichloro-4-fluorenemethanol（VI）. The final product（I） was obtained by further condensation of（VI） with p-chlorobenzaldehyde. RESULTS: Acetylation and chloroacetylation of III, the acetyl and chloroacetyl groups entered mainly into the 4 position of fluorene nucleus by both chemical method and spectrum analysis. CONCLUSION: The reliability of this new route of synthesis was established.