Convenient Synthesis of Tolcapone, a Selective Catechol‐O‐methyltransferase Inhibitor

  title={Convenient Synthesis of Tolcapone, a Selective Catechol‐O‐methyltransferase Inhibitor},
  author={G. Manikumar and Chunyang Jin and K. Rehder},
  journal={Synthetic Communications},
  pages={810 - 815}
Abstract A convenient and efficient synthesis of tolcapone from commercial 4‐benzyloxy‐3‐methoxybenzaldehyde is presented. Grignard reaction of 4‐benzyloxy‐3‐methoxybenzaldehyde (1) with p‐tolylmagnesium bromide followed by Oppenauer oxidation of the hydroxyl functionality and subsequent O‐debenzylation gave phenol 5. Compound 5 was regioselectively nitrated and then subjected to O‐demethylation to produce tolcapone in 60% overall yield. 
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