Patent EA-003948-B1 (EA)
Title: Method for producing derivatives of biphenyl-2-carboxylic acid
Inventor: SCHNEIDER HEINRICH
IPC: C07C63/331
Filed: 2000-02-12
Abstract: 1) Process for preparing biphenyl-2-carboxylic acid derivatives of general formula (I) wherein R<1> and R<2> which may be identical or different denote hydrogen, C1-C6-alkyl, which may optionally be substituted by halogen, C1-C6-alkoxy, C1-C6-acyl, C1-C6-alkoxycarbonyl, COOH, phenyl, benzyl, halogen, hydroxy, nitro or amino, or wherein R<1> and R<2> together with adjacent carbon atoms of the phenyl ring form a saturated or unsaturated 5- or 6membered carbocyclic group which may optionally be substituted by C1-C4-alkyl, halogen, COOH, phenyl or hydroxy; characterized in that a (2-oxazolinyl)-2-biphenyl derivative of general formula (IV) wherein R<1> and R<2> are as hereinbefore defined and R<OX> denotes an oxazolin-2-yl group, which may optionally be mono-, di-, tri- or tetra-substituted by one or more of the groups C1-C6-alkyl, which may optionally be substituted by halogen, hydroxy or C1-C4-alkoxy, C1-C6-alkoxy, phenyl, which may optionally be substituted by C1-C4-alkyl, C1-C4-alkoxy, hydroxy, nitro or amino, benzyl, pyridyl or C1-C6-alkoxycarbonyl, is saponified with hydrochloric acid at the temperature of 120 degree C-160 degree C under the pressure of 3-6 bar, in the presence of an inert organic solvent which is immiscible with water. 2) Process according to claim 1, wherein R<1> and R<2>, which may be identical or different, denote hydrogen, C1-C4-alkyl, which may optionally be substituted by fluorine, chlorine or bromine, C1-C4-alkoxy, C1-C4-acyl, C1-C4-alkoxycarbonyl, COOH, phenyl, benzyl, fluorine, chlorine, bromine, hydroxy, nitro or amino, or wherein R<1> and R<2> together with adjacent carbon atoms of the phenyl ring form an unsaturated 6-membered carbocyclic group which may optionally be substituted by C1-C4-alkyl, fluorine, chlorine, bromine, COOH, phenyl or hydroxy, and R<OX> denotes an oxazolin-2-yl group, which may optionally be mono- or disubstituted by one or more of the groups C1-C4-alkyl, which may optionally be substituted by fluorine, chlorine, bromine, hydroxy or C1-C4-alkoxy, C1-C4-alkoxy, phenyl, which may optionally be substituted by C1-C4-alkyl, C1-C4-alkoxy, hydroxy, nitro or amino, benzyl or C1-C4-alkoxycarbonyl. 3) Process according to claim 1 or 2, wherein R<1> and R<2>, which may be identical or different, denote hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, CF3, methoxy, ethoxy, COOH, phenyl, benzyl, fluorine, chlorine, bromine, hydroxy, nitro or amino, or wherein R<1> and R<2> together with adjacent carbon atoms of the phenyl ring form an anellated phenyl ring which may optionally be substituted by methyl, ethyl, n-propyl, isopropyl, tert-butyl, fluorine, chlorine, bromine, COOH, phenyl or hydroxy, and R<OX> denotes an oxazolin-2-yl group, which may optionally be mono- or disubstituted by one or more of the groups methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, methoxymethyl, hydroxymethyl, methoxy or ethoxy, or phenyl, which may optionally be substituted by methyl, ethyl, n-propyl, iso-propyl, n-butyl, tert.-butyl, methoxy, ethoxy or hydroxy, or benzyl, methoxycarbonyl or ethoxycarbonyl. 4) Process according to one of claims 1 to 3, wherein R<1> and R<2>, which may be identical or different, denote hydrogen, methyl, CF3, COOH, phenyl, fluorine or hydroxy, or wherein R<1> and R<2> together with adjacent carbon atoms of the phenyl ring form an anellated phenyl ring, and R<OX> denotes an oxazolin-2-yl group, which may optionally be mono- or di- substituted by one or more of the groups methyl, ethyl, methoxy-, ethoxy, phenyl or benzyl. 5) Process according to one of claims 1 to 4, wherein R<1> and R<2> which may be identical or different, denote hydrogen, methyl or CF3, and R<OX> denotes an oxazolin-2-yl group, which may optionally be mono-, or di- substituted by methyl. 6) Process according to one of claims 1 to 5, characterized in that saponification is carried out at a pressure of 4-5 bar. 7) Process according to one of claims 1 to 6, characterized in that 3.0 - 6.0 mol of hydrochloric acid are used for the saponification per mol of starting compound of general formula (IV). 8) Process according to one of claims 1 to 7, characterized in that 3.5 - 5.0 mol of hydrochloric acid are used for the saponification per mol of starting compound of general formula (IV). 9) Process according to one of claims 1 to 8, characterized in that aliphatic or aromatic hydrocarbons or aromatic chlorohydrocarbons with 6-10 carbon atoms are used as the organic solvent. 10) Process according to one of claims 1 to 9, characterized in that aliphatic or aromatic hydrocarbons with 7-8 carbon atoms or chlorobenzene are used as the organic solvent. 11) Process according to one of claims 1 to 10, characterized in that toluene, xylene, chlorobenzene and methylcyclohexane are used as the organic solvent. 12) Process according to one of claims 1 to 11, characterized in that methylcyclohexane is used as the organic solvent. 13) Process for preparing 4'-methylbiphenyl-2-carboxylic acid according to one of claims 1 to 12.