Patent EA-003058-B1 (EA)
Title: Process for intermediates for the manufacture of pyridine-2,3-dicarboxylate compounds
Inventor: WU WEN XUE
IPC: C07C229/30
Filed: 1999-06-11
Abstract: 1. A process for the manufacture of a compound of formula I   wherein R4 and R6 are each independently H, C1-C6alkyl, C1-C6alkenyl, phenyl or substituted phenyl; R5 is H; halogen; C1-C6alkyl optionally substituted with one or more C1-C4alkoxy groups; C1-C6alkenyl; phenyl or substituted phenyl; and R2 and R3 are each independently C1-C6alkyl, phenyl or substituted phenyl; which comprises reacting a compound of formula II or an alkali metal salt thereof   wherein X is O or S; R1 is C1-C6alkyl, phenyl or substituted phenyl; and R2 and R3 are as described for formula I; with at least one molar equivalent of a compound of formula III   wherein R4, R5 and R6 are as described for formula I; and an ammonia source in the presence of a solvent optionally at an elevated temperature. 2. The process according to claim 1 wherein the ammonia source is an ammonium salt. 3. The process according to claim 1 wherein the temperature is about 25 degree C - 185 degree C. 4. A process for the preparation of a compound of formula I   wherein R4 and R6 are each independently H, C1-C6alkyl, C1-C6alkenyl, phenyl or substituted phenyl; R5 is H; halogen; C1-C6alkyl optionally substituted with one or more C1-C4alkoxy groups; C1-C6alkenyl; phenyl or substituted phenyl; and R2 and R3 are each independently C1-C6alkyl, phenyl or substituted phenyl which comprises reacting a compound of formula IV   wherein X is O or S; R1 is C1-C6alkyl, phenyl or substituted phenyl; and R2 and R3 are as described for formula I with at least one molar equivalent α-β of unsaturated ketone of formula III   wherein R4, R5 and R6 are as described for formula in the presence of a solvent optionally at an elevated temperature. 5. The process according to claim 1 or 4 wherein X is O; R1 is methyl, ethyl or phenyl; R4 and R6 are each independently H; and R5 is H, methyl, ethyl or methoxymethyl. 6. The process according to claim 1 or 4 wherein the solvent is an aromatic hydrocarbon, an alkanol or a mixture thereof. 7. The process according to claim 6 wherein the solvent is toluene, ethanol or a mixture thereof. 8. A compound of formula IV   wherein X is O or S; R1 is C1-C6alkyl, phenyl or substituted phenyl; and R2 and R3 are each independently C1-C6alkyl, phenyl or substituted phenyl. 9. The compound according to claim 13 wherein X is O and R1 is methyl, ethyl or phenyl. 10. A process for the manufacture of a compound of formula V   wherein R4 and R6 are each independently H, C1-C6alkyl, C1-C6alkenyl, phenyl or substituted phenyl; and R5 is H; halogen; C1-C6alkyl optionally substituted with one or more C1-C4alkoxy groups; C1-C6alkenyl; phenyl or substituted phenyl which comprises: reacting a compound of formula II or the alkali metal salt thereof   wherein X is O or S; R1 is C1-C6alkyl, phenyl or substituted phenyl; and R2 and R3 are each independently C1-C6alkyl, phenyl or substituted phenyl with at least one molar equivalent of a compound of formula III   wherein R4, R5 and R6 are as described for formula V and an ammonia source in the presence of a solvent optionally at an elevated temperature to give a compound of formula I   wherein R2, R3, R4, R5 and R6 are described hereinabove; reacting said formula I compound with an amino amide of formula VI   in the presence of an inert solvent and a strong base to give the carboxylate salt of the desired formula V compound; and acidifying said carboxylate salt to give the desired free carboxylic acid compound of formula V.