DE102005042458A1 - Process for the preparation of 2-substituted carboxylic acids - Google Patents

Process for the preparation of 2-substituted carboxylic acids

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Publication number
DE102005042458A1
DE102005042458A1 DE200510042458 DE102005042458A DE102005042458A1 DE 102005042458 A1 DE102005042458 A1 DE 102005042458A1 DE 200510042458 DE200510042458 DE 200510042458 DE 102005042458 A DE102005042458 A DE 102005042458A DE 102005042458 A1 DE102005042458 A1 DE 102005042458A1
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formula
compound
preparation
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method according
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Eike Johannes Dr. Bergner
Klaus Dr. Ebel
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BASF SE
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BASF SE
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00Preparation of carboxylic acid esters
    • C07C67/03Preparation of carboxylic acid esters by reacting an ester group with a hydroxy group
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/09Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00Preparation of carboxylic acid esters
    • C07C67/30Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms

Abstract

The The present invention relates to a process for the preparation of in 2-position substituted tert-butyl esters by alkylation the corresponding tert-butyl ester enolates. The invention relates about that In addition, a method for producing the corresponding free carboxylic acids by acid hydrolysis of said tert-butyl esters and their implementation to further carboxylic acid esters.

Description

  • Technical field of the Invention:
  • The The present invention relates to a process for the preparation of in 2-position substituted tert-butyl esters by alkylation the corresponding tert-butyl ester enolates. The invention also relates a process for the preparation of the corresponding free carboxylic acids by acid hydrolysis of said tert-butyl ester and their implementation too further carboxylic acid esters.
  • The Alkylation of carboxylic acid esters by deprotonation with strong bases and trapping of the metal enolate with electrophiles represents an important transformation of the organic Synthesis chemistry. Deprotonation typically occurs at very low levels Temperatures, often at -78 ° C. To avoid undesirable Side reactions, especially the Claisenkondensation are usually only After addition of the electrophile, warm to room temperature, as by W. Dai, for example. in J. Org. Chem. 1993, 58, 1900-1908. Depending on the choice of non-nucleophilic base used are the Reaction mixture often complexing agents such as dimethylpropyleneurea (DMPU) or hexamethylphosphoric triamide (HMPT) added from the process as well as toxicological View are not safe.
  • 2-substituted isovaleric acids or their esters are in principle accessible in this way. she represent important intermediates for the production of active pharmaceutical ingredients represents.
  • The WO 01/09079 discloses a process for the preparation of 2-alkyl-5-halo-pent-4-enecarboxylic acids and their acid derivatives such as. their esters by alkylation of the corresponding Esterenolate with allyl halides. Beispeilhaft becomes the conversion of Isovaleriansäureethylester with lithium diisopropylamide to the corresponding ester enolate and subsequent reaction described with trans-1,3-dichloropropene. The reaction is in the presence of potassium iodide and DMPU as cosolvent at -20 ° C.
  • Dangyan, M. T. et al. describe in Izvest. Akad. Nauk Armyan. S.S.R., Khim Nauki 13, no. 4, 259-62 (1960); Chem. Abstracts 1961, 20950; the alkylation of 2-substituted malonic esters with 1,3-dichloropropene and subsequent decarboxylation saponification to the corresponding acids.
  • The US 4,492,799 discloses a process for the preparation of ethyl 4-chloro-2-isopropyl-4-pentenoate by deprotonation of ethyl isovalerate with lithium diisopropylpropamide and subsequent reaction with 2,3-dichloro-1-propene at temperatures from -78 ° C to -30 ° C. The target compound was obtained in a yield of 46% of theory receive.
  • R.J. Cregge et al. describe in Tetrahedron Lett. 26, 1973, 2425-2428 Process for the alkylation of esters by deprotonation with Lithiumdiisoprpylamid (LDA) at -78 ° C and subsequent alkylation in the presence of 0.3 equivalents of hexamethylphosphoric triamide.
  • M.W. Rathke et al. describe in Journal of the American Chemical Society, 93 (9), 1971, 2318-2320 the alkylation of tert-butyl acetate and hexanoate with various Alkylating agents at -78 ° C. The deprotonation the ester used is carried out at the same temperature means Lithium isopropylcyclohexylamide as the base.
  • Object of the invention:
  • in the Prior art light was that of the present invention underlying task in the provision of a method for the preparation of 2-substituted carboxylic acids or their esters, that under procedural advantageous Conditions, especially at temperatures that can be advantageously achieved and while avoiding unwanted Additives or solvents are carried out can. The formation of unwanted by-products should be as much as possible be avoided.
  • Description of the invention and the preferred embodiments:
  • The object has been achieved according to the invention by the provision of a process for the preparation of a compound of the formula (I)
    Figure 00020001
    in which
    R 1 is hydrogen or straight or branched C 1 - to C 6 -alkyl and
    R 2 is unbranched or branched C 1 - to C 6 -alkyl or C 1 - to C 6 -alkenyl or benzyl, where the radicals mentioned contain one or more identical or different substituents selected from the group of the substituents chlorine, bromine, iodine, Alkoxy, thioalkyl, dialkylamino, diarylamino and aryl may have
    means
    comprising the steps
    • a) reaction of a compound of the formula (II)
      Figure 00030001
      wherein R 1 has the same meaning as in formula (I), with a strong base other than lithium-isopropyl-cyclohexylamide, and
    • b) reaction of the intermediate product obtained in step a) with a compound of the formula (III) R 2 -X (III), wherein R 2 has the same meaning as in formula (I) and X represents chloro, bromo or iodo mesylate, tosylate, triflate, with the proviso that when R 1 is ethyl, the compound of formula (III) is not 1,3-dibromopropane is.
  • The process according to the invention enables the preparation of carboxylic acid tert-butyl esters of the formula (I)
    Figure 00030002
    where R 1 is hydrogen or unbranched or branched C 1 - to C 6 -alkyl and R 2 is unbranched or branched C 1 - to C 6 -alkyl or C 2 - to C 6 -alkenyl or benzyl wherein said radicals may have one or more identical or different substituents selected from the group consisting of substituents chlorine, bromine, iodine, alkoxy, thioalkyl, dialkylamino, diarylamino and aryl.
  • The term C 1 - to C 6 -alkyl are to be understood as meaning alkyl radicals having 1 to 6 carbon atoms, such as, for example: methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, Pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3 Methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl.
  • C 2 - to C 6 -alkenyl in the context of the present invention represents a mono- or polyethylenically unsaturated radical having 2 to 6 carbon atoms, such as, for example: ethenyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3 Butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl and 5-hexenyl. The radicals mentioned may, if possible, in each case in the cis or trans or the E or Z configuration with respect to the existing double bonds.
  • In the case of the radical R 2 , said radicals may have one or more, usually 1 or 2, identical or different substituents selected from the group of the substituents chlorine, bromine, iodine, alkoxy, thioalkyl, dialkylamino, diarylamino and aryl, preferably chlorine ,
  • In this case, alkoxy is preferably a C 1 -C 6 -alkyl radical bonded via an oxygen atom, as described above, particularly preferably methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentoxy or n-hexoxy. The term thioalkyl is preferably a radical bound via a sulfur, as described above C 1 - to C 6 alkyl. The term dialkylamino is to be understood as meaning amino substituents having two identical or different alkyl radicals, preferably C 1 -C 6 -alkyl radicals as described above, for example dimethylamino or diethylamino. In the context of the present invention, the term aryl denotes an aryl radical having 6 to 14 carbon atoms, preferably optionally substituted phenyl. The term diarylamino is understood to mean an amino substituent having two identical or different aryl radicals.
  • As in the context of the present invention preferred radicals R 1 may be mentioned:
    Isopropyl, isobutyl, tert-butyl, sec-butyl, most preferably isopropyl.
  • Preferred radicals R 2 according to the invention are chlorine-substituted propenyl radicals, for example 3-chloropropen-1-yl, 2-chloropropen-1-yl, 1-chloropropen-3-yl, 2-chloropropen-3-yl preferably trans-1-chloro-propen-3-yl.
  • The starting compounds to be used according to the invention are compounds of the formula (II)
    Figure 00050001
    wherein the radical R 1 has the same meaning as for the desired target compound of the formula (I).
  • In accordance with step a) of the process according to the invention, the starting compounds of Formula (I) with a strong base around. Bases which can be used in accordance with the invention are in principle all bases which are capable, ie strong enough, of converting a tert-butyl ester into its corresponding ester enolate, for example potassium hexamethyldisilazide, sodium hexamethyldisilazide, lithium hexamethyldisilazide, lithium diisopropylamide, lithium diethylamide, lithium di-tert-butylamide, lithium diadamantylamide, lithium -2,2,6,6, -tetramethylethylpiperidid.
  • Preferred strong bases according to the invention are metallated dialkylamines of the formula (IV) MNR 3 R 4 (IV), where M is lithium, sodium or potassium, preferably lithium and the radicals R 3 and R 4 are identical or different and are an unbranched, branched or cyclic C 1 - to C 6 -alkyl radical or a trialkylsilyl radical such as trimethylsilyl. Such metallated, preferably lithiated, dialkylamines can be prepared by methods known per se to the person skilled in the art, for example by treating a corresponding dialkylamine, such as, for example, diisopropylamine, diisobutylamine or isopropylcyclohexylamine, with a suitable lithium alkyl, for example n-butyllithium, s-butyllithium, tert. Butyllithium, n-hexyllithium, methyllithium or phenyllithium. Such processes are described in detail, for example, in "The Practice of the Organic Chemist", Gattermann, Wieland, newly edited by T. Wieland and W. Sucrow, 43rd ed., Berlin-New York, Walter de Gruyter Furthermore, solutions of such bases A particularly preferred strong base according to the invention is lithium diisoproylamine (LDA).
  • The Implementation according to step a) the present invention is advantageously carried out so that you have a solution of the chosen strong base, preferably the selected lithiated dialkylamine in a suitable solvent such as tetrahydrofuran, dioxane, dimethoxyethane, or others prepares cyclic or acyclic ethers. This is usually done at temperatures of about -80 ° C to about 0 ° C, preferred from about -60 ° C to about 0 ° C, especially preferably about -40 ° C to about 0 ° C and all more preferably about -20 ° C to about 0 ° C through Adding the chosen one organolithium reagent to the selected dialkylamine.
  • To the solution thus prepared the strong base then becomes common the chosen one Starting compound of the formula (I), if desired in the form of a solution in one of the abovementioned solvents. The Addition and subsequent reaction of the tert-butyl ester of the formula (I) with the chosen one Strong base is preferably carried out at temperatures of about -20 ° C to about 0 ° C. The starting compound of the formula (I) is thereby approximately equimolar to the chosen base, preferably in a molar ratio from about 0.9 to 1 to about 1.3 to 1. After a dripping time From about 10 minutes to about 1 hour, the formation of the ester enolate is usually quickly, usually after about 2 h, often completed after about 1 h.
  • In step b) of the process according to the invention, the intermediate product or product mixture obtained in step a) is reacted with a compound of the formula (III) R 2 -X (III), in which the radical R 2 has the same meaning as in the target compound of the formula (I) and X is chlorine, bromine or iodine, triflate, tosylate or mesylate, preferably chlorine.
  • Accordingly, the compounds of the formula (III) are alkyl or alkenyl halides having up to 6 carbon atoms or benzyl halides which may each have further substituents as described for the radical R 2 . Preferred compounds of the formula (III) according to the invention are allyl halides, in particular allyl chlorides such as, for example, allyl chloride, allyl bromide, 1,3-dichloropropene, 1,2-dichloropropene, 3-chloroallyl mesylate, 3-chlorallyl triflate, 3-chloroallyl tosylate, particularly preferably trans-1.3 -Dichlorpropen.
  • In the event that the radical R 1 in formula (I) or (II) is ethyl, corresponding to the reaction of tert-butyl n-butyrate, the group of the compounds of the formula (III) to be used according to the invention does not comprise the compound 1 , 3-dibromopropane.
  • The Implementation according to step b) is advantageously carried out so as to give the solution prepared in step a of deprotonated tert. Butyl esters the chosen compound of the formula (III) preferably at a temperature of about -20 ° C to about 0 ° C admits.
  • It may be advantageous to use the selected compound of the formula (III) in a slight molar excess with respect to the ester enolate or the starting compound of the formula (II), especially in a molar ratio of from about 1: 1 to about 2: 1, preferably about 1.05 to 1 to about 1.3 to 1. After addition of the compound of formula (III), the formation of the desired product of formula (I) in the above-mentioned temperature range is usually completed after about 1 to about 24 hours, often after about 3 to about 6 hours. The products or product mixtures obtained can subsequently be worked up, isolated or further processed by methods known to the person skilled in the art be cleaned.
  • The inventive reaction according to step b) can be successful with much avoidance in the context of alkylation reactions usual Complexing agents or co-solvents such as hexamethylphosphoric triamide (HMPT), Dimethyl propylene urea DMPU, tetramethylethylenediamine TMEDA, Pentamethyldiethylenetriamine, crown ethers, for. B. 15-crown-5, DMF, Potassium tert-butylate performed become. Preferably leads you the reaction in the presence of up to about 0.25 equivalents, more preferably of up to 0.2 and more preferably of up to about 0.1 equivalents, based on the molar amount of base used, by. As part of a preferred embodiment the method according to the invention you lead the implementation according to step b) without addition, particularly preferably in the absence of HMPT by.
  • In a preferred embodiment, the present invention relates to a process for the preparation of compounds of the formula (Ia)
    Figure 00070001
    wherein R 1 'may have the same meanings as R 1 in formula (I), preferably isopropyl and Z is chlorine, bromine or iodine, preferably chlorine, comprising the steps
    • a) reaction of a compound of the formula (II)
      Figure 00070002
      wherein R 1 'has the same meaning as in formula (Ia), with a strong base and
    • b) reaction of the intermediate product obtained in step a) with a compound of the formula (IIIa)
      Figure 00080001
      wherein Z has the same meaning as in formula (Ia) and Z 'may be the same or different from Z and chlorine, bromine or iodine, preferably iodine.
  • The so accessible tert-butyl ester of the formulas (I) or (Ia) can be easily submerged Influence of suitable acids or Lewis acids such as sulfuric acid, trifluoroacetic, methane, Acetic acid, hydrobromic, Zinc bromide, hydrochloric acid, formic acid, propionic into the corresponding free carboxylic acids, such as in "Protective Groups in Organic Synthesis ", T.W. Greene, P.G.M. Wuts, 1999, John Wiley & Sons, Inc. Canada, 404-408. Usually prepares to a solution of the corresponding tert-butyl ester in a suitable inert solvent such as toluene, methylene chloride, benzene, glacial acetic acid, ethylene glycol the chosen one Acid, usually in catalytic amount and heated if necessary until complete ester cleavage.
  • The so accessible carboxylic acids For their part, they can again be determined by methods known to the person skilled in the art esterify, for example under acid catalysis in the presence of a Alcohol.
  • Furthermore can be obtained from the tert-butyl esters obtainable according to the invention of the formula (I) also other esters by direct transesterification, i. without intermediary formation or isolation of the free carboxylic acid. For this purpose, the inventively produced Esters of the formula with the corresponding alcohol in the presence of an acid or Lewis acid implemented.
  • The present invention therefore also relates to a process for the preparation of carboxylic acids or carboxylic acid derivatives of the formula (V)
    Figure 00080002
    in which
    R 1 " , R 2" may have the meanings given for R 1 and R 2 in formula (I) and
    R 5 is hydrogen or a straight-chain, branched and / or cyclic C 1 - to C 12 -alkyl radical or C 7 - to C 12 -aralkyl radical
    comprising the steps
    • i) Preparation of a compound of formula (I) according to one of claims 1 to 7, and
    • ii) hydrolysis of the compound of the formula (V) obtained in step i) to the carboxylic acid of the formula (Va)
      Figure 00090001
      where the radicals R 1 " and R 2" have the meanings chosen for formula (I) in the presence of an acid or Lewis acid and
    • iii) optionally esterification of the carboxylic acid of the formula (Va) in the presence of an acid or Lewis acid and an alcohol of the formula (VII) R 5 OH (VII).
  • In this case, C 1 - to C 12 -alkyl denotes a straight-chain or branched alkyl radical having 1 to 12 carbon atoms, for example as mentioned above for C 1 - to C 6 -alkyl and furthermore also heptyl, octyl, nonyl, decyl, dodecyl. C 7 - to C 12 -aralkyl is a phenyl radical bound via an alkyl radical having at least one carbon atom, for example benzyl, 1-phenylethyl or 2-phenylethyl.
  • The inventive method opens accordingly an attractive access to substituted in 2-position carboxylic acids and their esters starting from the usually readily available tert-butyl esters. A particular advantage of the method according to the invention is to be emphasized that it is advantageous in terms of process technology and economically Conditions, especially while avoiding low temperatures as well while avoiding additional procedurally as well as toxicologically problematic reagents carry out leaves. It succeeds, the potential always occurring as a side reaction Self-condensation of the esters or ester enolates used largely to push back what especially higher in the synthesis refined products such as e.g. Pharmaceutical precursors of particular importance is.
  • The the following examples serve to illustrate the invention, without restricting it in any way:
  • Example 1: Preparation of (4E) -5-chloro-2-isopropyl-4-pentenoic acid tert-butyl ester
  • In 34.2 g (0.33 mol) of diisopropylamine were added to a flask under an inert gas atmosphere dissolved in 100 ml of tetrahydrofuran and cooled to -5 ° C. Subsequently, over 60 min 130.7 g (0.3 mol) of a 15 wt .-% solution of n-butyllithium in n-hexane added dropwise. After dosing 60 min at -5 ° C was stirred. After that became a solution of 44.4 g (0.28 mol) of tert-butyl 3-methylbutanoate in 40 ml Tetrahydrofuran was added dropwise within 30 min. After the complete addition was stirred for a further 15 min at -5 ° C. After that were 39.7 g (94% strength, 0.34 mol) of trans-1,3-dichloropropene were added dropwise. The entire reaction mixture was after the addition of trans-1,3-dichloropropene after 3 h at -5 ° C stirred. After that was added with 250 ml of 20% ammonium chloride solution and washed twice with extracted 125 ml of toluene. The combined organic phases were subsequently once washed with 125 ml of water and on a rotary evaporator was the solvent largely removed. There were 65.4 g of a crude product of (4E) -5-chloro-2-isopropyl-4-pentenoic acid tert-butyl ester as a yellow oil obtained with a content of 81.4 wt .-%. This corresponds to one Crude yield of 82%.
  • Example 2: Preparation of (4E) -5-chloro-2-isopropyl-4-pentenoic acid
  • It were 94.0 g of a 22.15 wt .-% solution of (4E) -5-chloro-2-isopropyl-4-pentenoic acid tert-butyl ester in toluene with 0.4 g sulfuric acid (98% pure, 0.004 mol). Subsequently was at 100 ° C for 6 hours heated. Thereafter, the solvent became removed on a rotary evaporator. There were 19.9 g of crude product a content of 71.75% by weight of (4E) -5-chloro-2-isopropyl-4-pentenoic acid. This corresponds to 99% crude yield.
  • Example: production of (4E) -5-chloro-2-isopropyl-4-pentenoic acid methyl ester
  • To a solution of 11.9 g (0.12 mol) of concentrated sulfuric acid in 100 g of methanol became 35 g (78 wt%, 0.12 mol) of (4E) -5-chloro-2-isopropyl-4-pentenoic acid tert -butyl ester and at 50 ° C heated. It was 12 h at 50 ° C stirred. To The reaction was brought to pH 7 with 68 g of 8% sodium hydroxide solution. Precipitated salts were dissolved by addition of 15 ml of water. Subsequently was extracted twice with 100 ml of toluene. The combined organic Extracts were over Dried sodium sulfate and concentrated on a rotary evaporator. It 20.8 g of (4E) -5-chloro-2-isopropyl-4-pentenoic acid methyl ester were obtained. This corresponds to a yield of 91%.

Claims (9)

  1. Process for the preparation of a compound of formula (I)
    Figure 00110001
    wherein R 1 is hydrogen or straight or branched C 1 - to C 6 -alkyl and R 2 is unbranched or branched C 1 - to C 6 -alkyl or C 1 - to C 6 -alkenyl or benzyl, where the radicals mentioned one or more identical or different substituents selected from the group of the substituents chlorine, bromine, iodine, alkoxy, thioalkyl, dialkylamino, diarylamino and aryl may have, comprising the steps a) reaction of a compound of formula (II)
    Figure 00110002
    where R 1 has the same meaning as in formula (I), with a strong base, except lithium isopropylcyclohexylamide, and b) reacting the product obtained in step a) with a compound of formula (III) R 2 -X (III), wherein R 2 has the same meaning as in formula (I) and X is chlorine, bromine, iodine, triflate, tosylate or mesylate, with the proviso that when R 1 is ethyl, the compound of formula (III) is not 1,3- Dibromopropane is.
  2. Process according to Claim 1 for the preparation of compounds of the formula (Ia)
    Figure 00120001
    where R 1 'can have the same meanings as R 1 in formula (I) and Z denotes chlorine, bromine or iodine, comprising the steps a) reaction of a compound of the formula (II)
    Figure 00120002
    where R 1 'has the same meaning as in formula (Ia), with a strong base and b) reacting the product obtained in step a) with a compound of formula (IIIa)
    Figure 00120003
    wherein Z has the same meaning as in formula (Ia) and Z 'may be the same or different from Z and represents chlorine, bromine or iodine.
  3. A method according to claim 2, characterized in that R 1 'is isopropyl.
  4. Method according to claim 2 or 3, characterized that Z and Z 'respectively Meaning chlorine.
  5. Method according to one of claims 1 to 3, characterized in that the strong base is a metalated dialkylamine of the formula (IV) MNR 3 R 4 (IV), where M is lithium, sodium or potassium and R 3 , R 4 are identical or different and are an unbranched, branched or cyclic C 1 - to C 6 -alkyl radical or a trialkylsilyl radical.
  6. Method according to one of claims 1 to 5, characterized that is used as a strong base lithium diisoproylamide.
  7. Method according to one of claims 1 to 6, characterized that it is carried out at a temperature of -20 ° C to 0 ° C.
  8. Process for the preparation of carboxylic acids or carboxylic acid derivatives of the formula (V)
    Figure 00130001
    where R 1 " , R 2" may have the meanings given for R 1 and R 2 in formula (I) and R 5 is hydrogen or a straight-chain, branched and / or cyclic C 1 - to C 12 -alkyl radical or C 7 - to C 12 aralkyl radical comprising the steps i) Preparation of a compound of formula (I) according to any one of claims 1 to 7, and ii) hydrolysis of the compound of formula (I) obtained in step i) to the carboxylic acid of the formula (Va )
    Figure 00140001
    wherein the radicals R 1 " and R 2" have the meanings chosen for formula (I) in the presence of an acid or Lewis acid and iii) optionally esterification of the carboxylic acid of formula (Va) in the presence of an acid or Lewis acid and an alcohol of the formula (VII) R 5 OH (VII).
  9. A method according to claim 8, characterized in that the steps ii) and iii) simultaneously and without isolation of the carboxylic acid of the formula (Va) performs.
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