The Synthetic Routes of Furo[2,3-b]pyridine-3-carboxaldehyde (9CI)

Furo[2,3-b]pyridine-3-carboxaldehyde (9CI) is a key intermediate in the synthesis of various organic compounds and pharmaceuticals.
It is widely used as a building block for the synthesis of heterocyclic compounds, and its demand is increasing in the pharmaceutical and agrochemical industries.
There are several synthetic routes to produce 9CI, and the choice of route depends on the desired yield, cost, and availability of starting materials.

One of the most common synthetic routes to 9CI is the Pinner reaction.
In this reaction, 2-bromo-3-methylpyridine (1) is treated with formaldehyde and sodium hydroxide to form 2,3-dimethyl-2,3-dihydro-1H-pyrrole-1,5-dione (2).
This intermediate is then treated with hydrogen chloride and sodium hydroxide to form 2,3-dimethyl-2,3-dihydro-1H-pyrrole-1,5-dione (2) and a triphenylmethane derivative (3).
The triphenylmethane derivative (3) is then treated with sodium hydroxide to form 4-chloro-3-methyl-1-phenyl-5H-pyrrole-1,4-dione (4).
Finally, 4-chloro-3-methyl-1-phenyl-5H-pyrrole-1,4-dione (4) is treated with hydrogen in the presence of a palladium catalyst to form 9CI.

Another common synthetic route to 9CI is the Pinkowski reaction.
In this reaction, 2,3-dibromopyridine (1) is treated with formaldehyde and sodium hydroxide to form 2,3-dimethyl-2,3-dihydro-1H-pyrrole-1,5-dione (2).
This intermediate is then treated with hydrogen chloride and sodium hydroxide to form 2,3-dimethyl-2,3-dihydro-1H-pyrrole-1,5-dione (2) and a triphenylmethane derivative (3).
The triphenylmethane derivative (3) is then treated with sodium hydroxide to form 4-chloro-3-methyl-1-phenyl-5H-pyrrole-1,4-dione (4).
Finally, 4-chloro-3-methyl-1-phenyl-5H-pyrrole-1,4-dione (4) is treated with hydrogen in the presence of a palladium catalyst to form 9CI.

Yet another synthetic route to 9CI is the Bock reaction.
In this reaction, 4-methyl-7-nitro-2,1,3-benzoxadiazole (1) is treated with sodium hydroxide to form 4-methyl-7-nitro-2,1,3-benzoxadiazol-5-one (2).
This intermediate is then treated with ammonia and hydrogen chloride to form 4-methyl-7-nitro-2,1,3-benzoxadiazol-5-one (2) and a triphenylmethane derivative (3).
The triphenylmethane derivative (3) is then treated with sodium hydroxide to form 4-chloro-3-methyl-1-phenyl-5H-pyrrole-1,4-dione (4).
Finally, 4-chloro-3-methyl-1-phenyl-5H-pyrrole-1,4-dione (4) is