Process for producing 2-substituted propionic acid
AssigneeNippon Petrochemicals Company, Limited
InventorsSaisuke Watanabe, Kazuharu Suyama
Life of this patent
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Abstract
Adipic acid diester is caused to react with alkoxide M(OR)n, wherein R is an alkyl group and M is an alkali metal or alkaline earth metal, the reaction product is successively subjected either to coupling with halomethylstyrene followed by carbonylation, or to coupling with 2-(halomethylphenyl)propionic acid or its ester followed by decarboxylation and hydrolysis. With this process, it is possible to produce more efficiently a specific 2-substituted propionic acid, loxoprofen.
Claims10
A process for producing a compound as represented by the following general formula II (hereinafter referred to as “compound II”):
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- wherein R′ represents an alkyl group having 4 or less carbon atoms, R″ represents hydrogen atom or an alkyl group having 4 or less carbon atoms, and R′ and R″ can be either the same or different, which process comprises the steps of:
- causing adipic acid diester to react with alkoxide as represented by the following general formula:
- M(OR)n
- wherein R represents an alkyl group having 5 or less carbon atoms, M represents alkali metal or alkaline earth metal, and n represents the number corresponding to the valence of M, and (OR)'s of n in number can be either the same or different,
- successively subjecting the product obtained above to coupling with halomethylstyrene to obtain a compound as represented by the following general formula I (hereinafter referred to as “compound I”):
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- wherein R′ represents an alkyl group having 4 or less carbon atoms, and
- causing said compound I to react with carbon monoxide and water or alcohol in the presence of metal catalyst to obtain said compound II.
A process for producing 2-substituted propionic acid as represented by the following general formula III (hereinafter referred to as “compound III”):
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- which process comprises the steps of (1-1) to (1-3):
- step (1-1) to cause adipic acid diester to react with alkoxide as represented by the following general formula:
- M(OR)n
- wherein R represents an alkyl group having 5 or less carbon atoms, M represents alkali metal or alkaline earth metal, and n represents the number corresponding to the valence of M and (OR)'s of n in number can be either the same or different,
- successively subjecting the product obtained above to coupling with halomethylstyrene to obtain the compound I as represented by the following general formula I:
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- wherein R′ represents an alkyl group having 4 or less carbon atoms,
- step (1-2) to cause said compound I to react with carbon monoxide and water or alcohol in the presence of metal catalyst to obtain the compound II as represented by the following general formula II:
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- wherein R′ represents an alkyl group having 4 or less carbon atoms, R″ represents hydrogen atom or an alkyl group having 4 or less carbon atoms, and R′ and R″ can be either the same or different,
- step (1-3) to subject said compound II to decarboxylation and hydrolysis to obtain said compound III.
A process for producing a compound II as represented by the following general formula II:
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- wherein R′ represents an alkyl group having 4 or less carbon atoms, R″ represents hydrogen atom or an alkyl group having 4 or less carbon atoms, and R′ and R″ can be either the same or different, which process comprises the steps of:
- causing adipic acid diester to react with alkoxide as represented by the following general formula:
- M(OR)n
- wherein R represents an alkyl group having 5 or less carbon atoms, M represents alkali metal or alkaline earth metal, and n represents the number corresponding to the valence of M and (OR)'s of n in number can be either the same or different,
- successively subjecting the product obtained above to coupling with a compound as represented by the following general formula IV (hereinafter referred to as “compound IV”) to obtain said compound II.
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- wherein X represents halogen atom, and R″ represents hydrogen atom or an alkyl group having 4 or less carbon atoms.
A process for producing 2-substituted propionic acid as represented by the following formula III (compound III):
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- which process comprises the steps of (2-1) and (2-2):
- step (2-1) to cause adipic acid diester to react with alkoxide as represented by the following general formula:
- M(OR)n
- wherein R represents an alkyl group having 5 or less carbon atoms, M represents alkali metal or alkaline earth metal, and n represents the number corresponding to the valence of M and (OR)'s of n in number can be either the same or different,
- successively subjecting the product obtained above to coupling with a compound IV as represented by the following general formula IV to obtain the compound II as represented by the general formula II:
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- wherein X represents halogen atom, and R″ represents hydrogen atom or an alkyl group having 4 or less carbon atoms, and
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- wherein R′ represents an alkyl group having 4 or less carbon atoms, R″ represents hydrogen atom or an alkyl group having 4 or less carbon atoms. R′ and R″ can be either the same or different, and
- step (2-2) to subject said compound II to decarboxylation and hydrolysis to obtain said compound III.
Dependencies are inferred from the claim text.