Processes and intermediates for synthesising opicapone

The method of any previous claim, wherein the acid anhydride is acetic anhydride or a halogenated derivative thereof, preferably acetic anhydride or trichloroacetic anhydride, more preferably acetic anhydride.

The method of any previous claim, wherein the nitration agent is in the form of an initial nitration solution.

The method of any previous claim, wherein the nitration agent is HNO3.

The method of any previous claim, wherein the nitration is carried out at a temperature from about 15 to about 60° C., preferably at a temperature from about 20 to about 45° C., more preferably at a temperature from about 25 to about 40° C., and optionally wherein the vanillic acid and/or acid anhydride and/or nitration agent are pre-heated before the nitration reaction.

The method of any previous claim, wherein the nitration reaction product is quenched with water.

The method of any previous claim, wherein the compound of formula (VI) is produced from vanillic acid in an overall yield of 50% or greater.

The method of any previous claim, wherein the compound of formula (VI) is precipitated, filtered and dried.

A solution of an acyl nitro-vanillic acid in an acid anhydride, preferably acetyl nitro-vanillic acid in acetic anhydride.

A solution of an acyl vanillic acid in an acid anhydride, preferably acetyl vanillic acid in acetic anhydride.