A convenient synthesis of codeine and morphine

Abstract

Abstract Acid‐catalysed cyclization of 1‐(3,5‐dihydroxy‐4‐methoxybenzyl)‐ N ‐formyl‐1,2,3,4,5,8‐hexahydro‐6‐methoxyisoquinoline ( 2c ), where the benzyl group is symmetrically substituted, gave N ‐formyl‐2‐hydroxynordihydrothebainone ( 4c ) exclusively. The 2‐hydroxyl substituent could be removed selectively in high yield, via the 1‐phenyltetrazol‐5‐yl ether ( 4d ), to yield N ‐formylnordihydrothebainone ( 4e) . (‐)‐ N ‐Formylnordihydrothebainone ( 4e ) was reduced to (‐)‐dihydrothebainone ( 4a) . The conversion of 4a to codeine ( 1b ) and morphine ( 1a ) has already been recorded.