Process for the preparation of pyridine-2,3-dicarboxylic acids
AssigneeCelgene Corporation
InventorsRandall A. Roehl, George W. Matcham, David I. Stirling
Life of this patent
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Abstract
Pyridine-2,3-dicarboxylic acids are prepared by the action of 2,3-dihydroxybenzoate-3,4-dioxygenase on 2,3-dihydroxybenzoic acids in a liquid medium which lacks active decarboxylase and which has a pH from 4 to 9, an ionic strength below about 1 molar, and a low concentration of metal cations and complex anions. In close temporal proximity, the 2-hydroxy-3-carboxymuconic acid semialdehyde which forms is allowed to react with a source of ammonia or a primary amine, avoiding substantial decarboxylation.
Claims13
Process for the preparation of pyridine-2,3-dicarboxylic acid of the formula:
- ##STR17## in which:
- R.sup.1 is hydrogen, alkyl of 1 to 12 carbon atoms, alkoxy of 1 to 12 carbon atoms, halogeno, mercapto, phenyl, or phenoxy;
- R.sup.2, taken independently of R.sup.3, is hydrogen, alkyl of 1 to 12 carbon atoms, alkoxy of 1 to 12 carbon atoms, halogeno, mercapto, phenyl, or phenoxy;
- and
- R.sup.3, taken independently of R.sup.2, is hydrogen or alkyl of 1 to 12 carbon atoms, unsubstituted or substituted with halogeno or alkoxy of 1 to 12 carbon atoms, or R.sup.2 and R.sup.3, taken together, are the residue of an aromatic ring fused to the depicted pyridine ring which comprises subjecting a 2,3-dihydroxybenzoic acid of the formula:
- ##STR18## in which R.sup.1, R.sup.2, and R.sup.3 are as herein defined, to the action of 2,3-dihydroxybenzoate-3,4-dioxygenase in a liquid medium lacking active decarboxylase and having a pH from 4 to 9, an ionic strength below about 1 molar, and a low concentration of metal cations and complex anions, to accumulate 2-hydroxy-3-carboxymuconic acid semialdehyde, and in sufficiently close temporal proximity to avoid substantial decarboxylation, reacting the 2-hydroxy-3-carboxymuconic acid semialdehyde thus formed with a source of ammonia or a primary amine.
Dependencies are inferred from the claim text.