Process for the production of 4-substituted acetoacetic acid...

C - Chemistry – Metallurgy – 07 – C

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C07C 69/72 (2006.01) C07C 67/343 (2006.01) C07C 69/716 (2006.01) C07C 69/738 (2006.01) C07D 211/32 (2006.01) C07D 295/18 (2006.01)

Patent

CA 1233823

ABSTRACT OF THE DISCLOSURE A process is disclosed for the production of 4- substituted acetoacetic acid derivatives of the formula: Image (IA) or Image (IB) wherein R is alkoxy having 1 to 6 C atoms, phenoxy, -NR'2, wherein R' is alkyl having 1 to 6 C atoms or aryl, or NR'2 which is azetidine, pyrrolidine or piperidine; and R1 and R2 are each hydrogen, alkyl, alkenyl, alkinyl or aryl. An acetoacetic acid derivative having the formula: Image wherein R is alkoxy having 1 to 6 C atoms, phenoxy, -NR'2, wherein R' is alkyl having 1 to 6 C atoms or aryl, or NR'2, which is azetidine, pyrrolidine or piperidine, is treated with a secondary amine at an elevated temperature and in the presence of an organic solvent. The water formed is separated and the intermediate is converted into the corresponding 3-enamine carboxylic acid derivative. The derivative is converted by treatment with sodium amide in liquid ammonia into the corresponding sodium salt. The sodium salt is thereafter converted by treatment with a halogen compound having the formula R1CH2X or R1R2CHX, wherein R1 and R2 are each hydrogen, alkyl, alkenyl, alkinyl or aryl and X is chlorine, bromine or iodine, into the corresponding 4-substituted enamino derivative, which is then hydrolyzed into the desired 4-substituted aceto- acetic acid derivative.

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