A new route to Roflumilast, a selective phosphodiesterase type 4 (PDE 4) inhibitor,
is described. The synthetic procedure starts from 4-hydroxy-3-iodobenzoic acid to
access the key intermediate 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic acid
via copper-catalyzed hydroxylation and utilizes amide coupling to accomplish the synthesis
of Roflumilast in 80% overall yield.
Key words
Roflumiast - PDE4 inhibitor - preparation - hydroxylation - copper catalyzed