Continuous flow synthesis method for the manufacture of isoniazid

A multistep continuous microreactor flow synthesis method for the manufacture of isonicotinyl-hydrazide of Formula 1

• comprising the steps of:
• a) in a first microreactor, or a first part of a suitable microreactor setup, reacting 4-cyano pyridine of Formula 12
• in a mixture of water and alcohol, with NaOH in a molar ratio of 4-cyano pyridine:NaOH of about 1:0.2 to about 1:0.4 at a temperature of about 95° C. to about 105° C. to produce the intermediate isonicotinamide of Formula 13
• b) in a second microreactor, or a second part a suitable microreactor setup, which is in fluid communication with the first microreactor, or the first part of the microreactor, reacting the intermediate isonicotinamide of Formula 13 with hydrazine hydrate in a molar ratio of 4-cyano pyridine:hydrazine hydrate of about 1:1.75 to about 1:2.50 at a temperature of about 100° C. to about 120° C.,
• wherein the reaction in step a) has a residence time of about 10 to about 32 minutes, the reaction in step b) has a residence time of about 10 to about 25 minutes, and the method produces the isonicotinyl-hydrazide of Formula 1 in yields greater than about 90%.