A concise flow synthesis of efavirenz.
Efavirenz is an essential medicine for the treatment of HIV, which is still inaccessible to millions of people worldwide. A novel, semi-continuous process provides rac-Efavirenz with an overall yield of 45%. This streamlined proof-of-principle synthesis relies on the efficient copper-catalyzed formation of an aryl isocyanate and a subsequent intramolecular cyclization to install the carbamate core of Efavirenz in one step. The three-step method represents the shortest synthesis of this life-saving drug to date.
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam (Germany).
Camille A
CA
Correia
Kerry
K
Gilmore
D Tyler
DT
McQuade
Peter H
PH
Seeberger
D000480:Alkynes; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry; D048588:Benzoxazines / Q000138:chemical synthesis* / Q000737:chemistry; D002219:Carbamates / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D003500:Cyclization; D003521:Cyclopropanes; D017953:Isocyanates / Q000737:chemistry
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D002219:Carbamates; D003521:Cyclopropanes; D017953:Isocyanates; D003300:Copper; C098320:efavirenz
API synthesis; carbamates; copper; flow chemistry; homogeneous catalysis