Synthetic entries to 6‐fluoro‐7‐substituted indole derivatives

Three practical synthetic entries of functionalized 6‐fluoro‐7‐substituted indole derivatives were developed in connection with the preparation of 7‐fluoro‐8‐substituted‐1,3,4,9‐tetrahydropyrano[3,4‐ b ]indole‐1‐acetic acid derivatives 11 . The first route, which permits group modification about position 8 of the pyranoindole skeleton, employs 2‐bromo‐3‐fluoroaniline ( 18 ) as a key intermediate, the preparation of which was achieved by either a novel ortho metalation of 15 or via the intermediacy of 22 . The second route utilizes 32 to append a terminally functionalized three carbon side chain onto the indole template and in addition leads to 43 from 40 . The third route to the 7‐fluoro‐8‐substituted‐pyranoindole skeleton complements route two in that the synthetic pathway exploits 32 in a nucleophilic fashion to construct a terminally functionalized two carbon appendage onto the indole nucleus.