ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Synthesis of 1-fluoro-substituted codeine derivatives

Sándor Hosztafi and János Marton

Institute of Pharmaceutical Chemistry, Semmelweis Medical University, HÖgyes Endre utca 9, H-1092 Budapest, Hungary

E-mail: hosztafi.sandor@pharma.semmelweis-univ.hu

Abstract: Syntheses of new N-demethyl-N-substituted analogues (propyl, allyl) of 1-fluorocodeine and their 7,8-dihydro derivatives were described starting from codeine. 1-Fluoronorcodeine and 1-fluorodihydronorcodeine were prepared by N-demethylation with α-chloroethyl chloroformate from the corresponding 6-O-acetyl protected derivatives. 3-O-Demethylation of 1-fluorocodeine and 1-fluorodihydrocodeine with boron tribromide resulted in 1-fluoromorphine and 1-fluorodihydromorphine respectively. 1-Fluorodihydromorphine was acetylated to 3,6-di-O-acetyl-1-fluorodihydromorphine. 8-Fluoroapocodeine and N-propyl-8-fluoroapocodeine were synthesized from the appropriate 1-fluorocodeine derivatives by acid-catalyzed rearrangement.

Keywords: 1-fluorocodeine analogs – 1-fluoromorphine – 1-fluorodihydromorphine – 8-fluoroapocodeine

Full paper is available at www.springerlink.com.

DOI: 10.1515/chempap-2016-0033

Chemical Papers 70 (7) 973–982 (2016)