FR2701706A1 - Process for the hydrolysis of alpha -chiral alpha -substituted carboxylic esters - Google Patents

Abstract

The subject of the present invention is a process for the hydrolysis of alpha -chiral alpha -substituted carboxylic esters for the purpose of the preparation of alpha -chiral alpha -substituted carboxylic acids. The invention relates in particular to the hydrolysis of alpha -chiral carboxylic esters substituted in the alpha -position by a halogen atom and derived from a furanose resulting from sugar, in order to obtain alpha -chiral alpha -halogenated carboxylic acids and more preferentially optically active 2-halopropionic acids. The distinguishing feature of the process of the invention is to carry out the hydrolysis of an alpha -halogenated ester derived from a furanose resulting from a sugar with an inorganic acid, in aqueous/organic medium.

Description

HYDROLYSIS PROCESS FOR CARBOXYL ESTERS
a-SUBSTITUES a-CHIRAUX.

 The present invention relates to a process for the hydrolysis of? -Substituted? -Chiral carboxylic esters for the preparation of? -Substituted? -Substituted carboxylic acids. In particular, the invention relates to the hydrolysis of α-chiral carboxylic esters substituted at the α-position by a halogen atom and derived from a furanose derived from a sugar, in order to obtain α-chiral α-halogenated carboxylic acids. and more preferably, 2-halogenopropionic acids optically active.

For twenty years, one seeks to control the stereochemistry of chemical reactions. Obtaining an enantiomerically pure molecule is motivated by the fact that the biological activity of a compound can be intimately related to its enantiomeric purity. Thus, 2-chloropropionic acid is a key intermediate in the synthesis of important herbicides such as (R) -2aryloxypropionic acids and their derivatives. The interest of selectively preparing the form
R is that said compound is active at doses less than half the corresponding racemic compounds. This gives rise to a major interest in safeguarding the environment.

dans laquelle R représente un radical méthyle, isopropyle, n-butyle ou isobutyle et R* représente le motif suivant:

- puis à saponifier le chloro-2 ester obtenu par l'hydroxyde de lithium, dans un mélange acétonitrile, ligroïne et eau en quantités volumiques égales.L. Duhamel et al have described in Synlett, p. 807, November 1991, the preparation of optically enriched 2-chloro-alkanoic acids of the (S) -configuration, by a process which consists of: chlorinating with N chlorosuccinimide, a silylated ketene acetal of formula:

in which R represents a methyl, isopropyl, n-butyl or isobutyl radical and R * represents the following unit:

and then saponifying the chloro-2 ester obtained with lithium hydroxide in an acetonitrile, ligroin and water mixture in equal volume amounts.

avec le chlorure de triméthylsilyle, en présence de diisopropylamidure de lithium.The silylated ketene acetal is obtained by reaction of:

with trimethylsilyl chloride in the presence of lithium diisopropylamide.

 Said process makes it possible to obtain a (S) -2-chloroalkanolic acid with a yield expressed relative to the ester represented above, of 65-72% but the enantiomeric excess caps at 90%.

 It has now been found and this is the object of the present invention, a method of hydrolysis faster than the previous, non-racemizing, with conservation of the configuration.

 The subject of the present invention is therefore a process for the hydrolysis of an α-halogenated ester derived from a furanose derived from a sugar, characterized in that it consists in hydrolysing said ester with a mineral acid in a hydroorganic medium.

dans laquelle les différents symboles représentent:
- R représente un radical hydrocarboné ayant de 1 à 40 atomes de carbone
qui peut être un radical aliphatique, saturé ou insaturé, linéaire ou ramifié;
un radical cyclique, saturé, insaturé ou aromatique, monocyclique ou
polycyclique; un radical cycloaliphatique- ou arylaliphatique, saturé ou
insaturé, linéaire ou ramifié; un atome d'halogène, de préférence un atome
de fluor, de chlore ou de brome,
- R* représente un radical dérivé d'un motif tétrahydrofuranyle,
- X représente un atome d'halogène, de préférence un atome de chlore ou
de brome différent de R, - avec un acide minéral, en milieu hydro-organique.More specifically, the process of the invention consists in reacting: an α-chiral halogenated ester corresponding to the following formula (I):

in which the different symbols represent:
R represents a hydrocarbon radical having from 1 to 40 carbon atoms
which may be an aliphatic radical, saturated or unsaturated, linear or branched;
a cyclic radical, saturated, unsaturated or aromatic, monocyclic or
polycyclic; a cycloaliphatic or arylaliphatic radical, saturated or
unsaturated, linear or branched; a halogen atom, preferably an atom
fluorine, chlorine or bromine,
R * represents a radical derived from a tetrahydrofuranyl unit,
X represents a halogen atom, preferably a chlorine atom or
bromine other than R, with a mineral acid, in a hydro-organic medium.

 The a-chiral α-halogenated esters which are more particularly involved in the process of the invention correspond to formula (I) in which R represents an aliphatic radical or a cycloaliphatic or arylaliphatic radical.

 More specifically, R may represent an alkyl, alkenyl, alkadienyl or alkynyl radical, linear or branched, preferably having from 1 to 24 carbon atoms.

dans ces formules R5 représente l'hydrogène ou un radical alkyle linéaire ou ramifié ayant de 1 à 4 atomes de carbone, de préférence, un radical méthyle ou éthyle,
- et/ou porteuse de l'un des substituants suivants:

dans ces formules, R5 ayant la signification donnée précédemment.The hydrocarbon chain can be optionally:
- interrupted by one of the following groups:

in these formulas R5 represents hydrogen or a linear or branched alkyl radical having from 1 to 4 carbon atoms, preferably a methyl or ethyl radical,
and / or carrier of one of the following substituents:

in these formulas, R5 having the meaning given above.

 The acyclic aliphatic, saturated or unsaturated, linear or branched may optionally carry a cyclic substituent. By ring is meant a saturated, unsaturated or aromatic carbocyclic ring, for example a cyclohexyl, phenyl or naphthyl radical.

dans ces formules R5 ayant la signification donnée précédemment.The acyclic aliphatic residue may be linked to the ring by a valency bond or by one of the following groups:

in these formulas R5 having the meaning given above.

 Among the aliphatic radicals optionally substituted by a ring, the preferred radicals are the following: a linear or branched alkyl radical having from 1 to 12 carbon atoms, a cycloalkylalkyl radical preferably having from 1 to 4 carbon atoms in the alkyl chain; a phenylalkyl radical having, preferably, from 1 to 4 carbon atoms in the alkyl chain.

 The oc-halogenated α-chiral esters more particularly involved in the process of the invention correspond to formula (I) in which R represents a cycloaliphatic, saturated, unsaturated or aromatic, monocyclic or polycyclic radical, preferably bicyclic.

 As more specific examples of carbocyclic R radicals, there may be mentioned, inter alia: an optionally substituted cycloalkyl radical preferably having from 5 to 7 carbon atoms, an optionally substituted phenyl radical, an optionally substituted naphthyl radical.

 The present invention does not exclude the presence of substituents on any ring intervening in the radical R, insofar as these do not interfere at the level of the hydrolysis reaction. As examples of substituents which may be carried by the ring, there may be mentioned, inter alia, linear or branched alkyl radicals, preferably having 1 to 4 carbon atoms, linear or branched alkoxy radicals, preferably having from 1 to 4 carbon atoms.

 Examples of preferred radicals R include the following radicals: methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclohexyl radical, phenyl and tolyl radicals, xylyl or naphthyl optionally carrying linear or branched alkyl radicals having 1 to 4 carbon atoms or alkoxy radicals having 1 to 4 carbon atoms, - the benzyl radical, phenylethyl.

 Among all the aforementioned R radicals, the invention is particularly applicable to compounds of formula (I) in which R represents a linear or branched alkyl radical having from 1 to 12 carbon atoms and preferably from 1 to 4 carbon atoms .

dans ladite formule (Il): - R1, R21 identiques ou différents, représentent un radical alkyle linéaire ou ramifié ayant de 1 à 12 atomes de carbone, un radical cyclohexyle, un radical phényle ou un radical benzyle, - R3, R4, identiques ou différents, représentent un radical alkyle linéaire ou ramifié ayant de 1 à 12 atomes de carbone, un radical cyclohexyle, un radical phényle ou un radical benzyle, - les radicaux R1 et R2 d'une part, R3 et R4 d'autre part, peuvent former ensemble un cycle à 5 chaînons (dioxolanne) ou à 6 chaînons (1,4-dioxanne).As regards the radical R * involved in α-chiral halogen compounds it comprises the furanose unit derived from a sugar. II represents more particularly a radical corresponding to the following formula (II):

in said formula (II): R1, R21, which are identical or different, represent a linear or branched alkyl radical having from 1 to 12 carbon atoms, a cyclohexyl radical, a phenyl radical or a benzyl radical, R3, R4, which are identical or different, represent a linear or branched alkyl radical having from 1 to 12 carbon atoms, a cyclohexyl radical, a phenyl radical or a benzyl radical, - the radicals R1 and R2 on the one hand, and R3 and R4 on the other, can together form a 5-membered (dioxolan) or 6-membered (1,4-dioxane) ring.

 The furanose motif can be derived from glucose but also from many other sugars such as allose, altrose, mannose, galactose, talose, gulose, idose, ribose, arabinose, xylose and lyxosis.

 The preferred motif chosen in the process of the invention is derived from glucose.

The preferred radical R * is therefore the following:

par réaction dudit acétal avec un N-halogénosuccinimide (N-bromosuccinimide ou N-chlorosuccinimide) dans un solvant organique.Examples of α-chiral α-halogenated esters preferably used in the process of the invention include, in particular, esters derived from a furanose unit carrying a free OH in the 3-position and one of the alkanoic acids. α-halogenated compounds: - 2-chloropropionic acid - 2-bromo propionic acid - 2-chloro-butanoic acid - 2-bromo-butanoic acid - 2-chloro-3-methyl-butanoic acid - 2-bromo-3-methylbutanoic acid - 2-chloro-3,3-dimethylbutanoic acid - 2-bromo 3,3-dimethylbutanoic acid - 2-chloro hexanoic acid - 2- hexanoic bromo - 2-chloro-4-methylpentanoic acid - 2-bromo-4-methylpentanoic acid
The process of the invention is quite suitable for the preparation of α-chiral α-halogenated esters derived from a furanose unit bearing a free OH in the 3-position and one of the following α-halogenated alkanoic acids: 2-chloro-propionic acid - 2-chloro-3-methylbutanoic acid - 2-chloro-4-methylpentanoic acid - 2-bromo-4-methylpentanoic acid
A preferred mode of synthesis of α-chiral α-halogenated esters of formula (I) as starting materials in the process of the invention consists in selectively halogenating an O-silyl ketene acetal corresponding to the following formulas:

by reacting said acetal with N-halosuccinimide (N-bromosuccinimide or N-chlorosuccinimide) in an organic solvent.

 In formulas (III) or (III) 'of said acetals, R and R * have the meaning given above and the different radicals R6, which may be identical or different, represent a hydrocarbon radical. Preferably, R6 represents a linear or branched alkyl radical having 1 to 4 carbon atoms or a phenyl radical. Preferably, R6 represents a methyl radical.

 The acetal ketene concentration is advantageously between 0.05 and 0.5 M.

 The amount of halogenating agent, expressed as the molar ratio between the halogenating agent and the ketene acetal, may be in the range of from 1 to 3.0, and is preferably in the region of 1.5.

The halogenation reaction is conducted in an organic solvent which preferably does not exhibit too high polarity. Suitable organic solvents are preferably those whose dielectric constant (measured at 25.degree. C.) is less than or equal to 10. As examples of solvents, mention may be made, inter alia, of dichloromethane or trichloromethane. carbon tetrachloride, toluene, diethyl ether, tetrahydrofuran,
Ethyl acetate.

 The temperature of the reaction is chosen between -10 ° C. and -100 ° C., preferably between -70 ° C. and -90 ° C.

 The halogenating agent is preferably introduced in solid form.

 With regard to O-silyl ketene acetals, they are known products described in the literature. They can be synthesized according to the procedure used by L. DUHAMEL et al (loc cit).

 Said method consists in carrying out the following steps: step 1: coupling at 20 ° C. of the carboxylic acid of formula R-CH 2 -COOH with the chiral auxiliary R * OH, with dicyclohexylcarbodiimide (DCC) and in the presence of a catalytic amount (10%) of N, N-dimethylaminopyridine in dichloromethane medium; step 2: reaction of the obtained ester R-CH 2 -COOR * with a silicon compound of formula (R 6) 3 SiCl at -70 ° C. in the presence of a base (a lithium amide and preferably lithium diisopropyl amide) to obtain the O-silyl ketene acetal corresponding to the formulas (lit) and (lit) '.

 According to the process of the invention, an α-chiral halogenated ester is hydrolyzed in the presence of a mineral acid.

 As examples of mineral acids, the following mineral acids are preferably used: hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid. Hydrochloric acid is the acid chosen preferentially.

 The normality of the aqueous solution used is advantageously less than 5 N and preferably between 1 and 3 N.

 The amount of mineral acid used relative to the bonded ester of formula (I) is generally at least equal to the stoichiometry of the reaction.

 When it is expressed by the ratio between the number of H + ions provided by the mineral acid and the number of moles of bonded ester of formula (I), it may vary between 1 and 20, preferably between 2 and 10 .

 The reaction is advantageously carried out in a hydro-organic medium.

 The volume ratio between water and the organic solvent may vary, for example, from 0.3 to 3.0.

 The choice of the organic solvent and the water / organic solvent ratio is determined in such a way that the reaction medium obtained is homogeneous.

As examples of organic solvents that are suitable for the present invention, mention may be made more particularly of: aliphatic alcohols such as ethanol, propanol, isopropanol, butanol,
Isobutanol, hexanol, ethylene glycol, ketones such as acetone, diethyl ketone, methyl ethyl ketone, diacetone alcohol, 2,5-hexanedione.

 The preferred solvents are acetone and diacetone alcohol.

 It is possible to use a mixture of organic solvents.

 The concentration of the ester of formula (I) in the reaction solvent (water + organic solvent) is such that it varies between 0.01 and 2 mol / liter, preferably between 0.1 and 0.5 mol / liter.

 As for the temperature of the hydrolysis reaction, it is advantageously chosen between 50 ° C. and 100 ° C. For convenience, the preferred temperature is the reflux temperature of the reaction mixture.

 According to a practical embodiment of the invention, the ester is introduced into the organic solvent, then the aqueous solution of the mineral acid is introduced and the reaction medium is brought to the chosen temperature.

 At the end of the reaction, the halogenated carboxylic acid a-chiral is recovered by any known means.

 A mode of separation used preferably consists of recovering in the organic phase, the halogenated carboxylic acid a-chiral. For this purpose, the reaction medium is treated with an organic solvent which may be chosen, for example, from the following organic solvents: aliphatic or aromatic halogenated hydrocarbons, and there may be mentioned: perchlorinated hydrocarbons, such as in particular tetrachloride, carbon, tetrachlorethylene, hexachloroethane, hexachloropropene and hexachlorobutadiene, partially chlorinated hydrocarbons such as methylene chloride, dichloroethane, tetrachloroethane, trichlorethylene, 1-chlorobutane, 1,2-dichlorobutane ; monochlorobenzene, 1,2-dichlorobenzene, 1,3-dichlorobenzene, 1,4-dichlorobenzene or mixtures of different chlorobenzenes; monobromobenzene or mixtures of monobromobenzene with one or more dibromobenzenes, aliphatic or aromatic ether-oxides and, more particularly, diethylether, dipropylether, diisopropylether, dibutylether, methyltertiobutylether, dipentylether, diisopentylether, oxide methyl and tert-butyl, ethyl tert-butyl ether, diphenyl ether; Petroleum ether; dibenzyl ether, anisole, phenetole, dimethoxybenzene, veratrole, aliphatic esters such as, in particular, methyl acetate, ethyl acetate and propyl acetate.

 One or more washes of the organic phase can be carried out, for example, from one to three. The washing is preferably carried out with water.

 The α-chiral halogenated carboxylic acid is thus recovered in said organic solvent.

 The α-chiral halogenated carboxylic acid can be separated by any known means, in particular by distillation under reduced pressure or by means of its sodium or potassium salt.

 The process of the invention makes it possible to conduct the hydrolysis of the halogenated ester without racemization.

The chiral auxiliary is, in general, destroyed in the hydrolysis conditions. Nevertheless, the process of the invention is very interesting when
An inexpensive chiral auxiliary is used because the means used to perform the hydrolysis are very accessible and inexpensive and their implementation can largely compensate for the costs incurred by the destruction of the chiral auxiliary.

 The following examples illustrate the invention without limiting it.

In the examples, the different symbols have the following meaning:
number of moles of halogenated carboxylic acid obtained
O-halogenated acid yield = -
number of moles of 1,2,5,6-di-O- (1-methyl)
Ethylidene) -oc-D-glucofuranosyl introduced
nb of moles of (S) - nb of moles of (R)
Energetic excess ee = ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
nb of moles of (S) + nb of moles of (R)
Nb of moles of (S) means number of moles of halogenated carboxylic acid of configuration (S).

Nb of moles of (R) means number of moles of halogenated carboxylic acid of (R) configuration.

nb of moles of (S) - nb of moles of (R)
Diastereomeric excess ed =
nb of moles of (S) + nb of moles of (R)
Number of moles of (S) means number of moles of halogenated ester (I) of (S) configuration for the carbon carrying the halogen.

Nb of moles of (R) means number of moles of halogenated ester (I) of (R) configuration for the carbon carrying the halogen.

 In the following examples, the halogenated carboxylic acid is an alkanoic acid.

EXAMPLES
The following is the operating protocol which is used in the examples.

 In the examples, the various analyzes are carried out by gas chromatography carried out on Hewlett-Packard 5890 series II gas chromatograph, equipped with an HP 3396 series Il integrator printer with a column A: HP1, 1 = 5 m, e = 0.53 mm, stationary phase = methylsilicone, Tnj = Tdet = 200 ° C., flow rate in He = 10 ml / min.

For the determination of "ed", the column used is the following: - column B: HP1, I = 25 m, = 0.25 mm, stationary phase = methylsilicone,
Tinj = Tdet = 210 C, flow rate in He = 1 ml / min with split = 1/15
For the determination of "ee", the column used is the following: - column C: Chirasil-L-Val, I = 25 m, e = o, 25 mm, Tnj = Tdet = 2oOXCs flow in
He = 1 ml / min with split = 1/15
Rotational powers were measured using a Perkin polarimeter
Elmer 241.

The ee are determined by polarimetry and GPC of the corresponding N-butyl amide (column C), prepared as follows according to the procedure of K. Watabe et al. (Synthesis 1987, 225). 10 mg of ahalogenated acid are placed in an excess of thionyl chloride (1 ml) at room temperature overnight or at 40 ° C. for 2 hours. The excess thionyl chloride is then evaporated and the residue taken up in 0.5 ml of anhydrous ether. The solution is cooled to 0.degree. C. and 1.2 ml of a 2% solution of tert-butylamine in dry ether are added dropwise thereto. After 30 minutes, the solvent is evaporated and the residue is taken up in a small amount of ether, filtered and evaporated. The tert-butylamide formed is dissolved in CH 2 Cl 2 and injected into CPG (column
C).

I) Synthesis of 1, 2: 5,6-di-O- (1-methylethylidene) -α-D-glucofuranosyl alkanoates
Starting from an alkanoic acid of formula R - CH 2 --COOH, the nature of the radical R is specified in the summary table (Table I).

 To 60 mmol of alkanoic acid dissolved in 50 ml of dry dichloromethane, 5 mmol of 4-N, N-dimethylaminopyridine and 50 mmol of 1,2,5,6-di-O- (1-methylethylidene) are added successively. aD-glucofuranose. After having cooled to 0 ° C., 60 mmol of dicyclohexylcarbodiimide in solution in 60 ml of dry dichloromethane are added.

 The dicyclohexylurea is filtered and the filtrate is concentrated. The residue taken up in 60 ml of ethyl acetate is filtered again. The filtrate is washed with 50 ml of water, three times 50 ml of a saturated solution of NaHCO 3, and 50 ml of a saturated solution of NaCl. The organic phase is dried over MgSO4. It is concentrated and purified by chromatography, the residue on silica (eluent = ethyl acetate / petroleum ether: 10/90).

The synthesized esters are characterized in IR by a band (c = 0) at 1740 cm -1
Infra-red spectra were recorded on the Perkin spectrometer
Elmer 16PC FTIR.

II) Synthesis of ketene acetals
7.5 mmol of diisopropylamine are placed in 15 ml of anhydrous tetrahydrofuran (THF) at 0 ° C. 7.5 mmol of n-butyllithium (2.5 M in hexane) are added and the mixture is stirred for 15 minutes at 0 ° C. The mixture is cooled to -70.degree. C. and 7.5 mmol of ClSiMe.sub.3 and then of 5 mmol of ester in solution in 2 ml of THF are added successively in the course of 6 minutes (with the syringe pump). After addition, the mixture is kept at -70.degree. C. for 3 hours, before allowing the reaction medium to slowly return to room temperature (3h to pass from -70.degree. C. to 0.degree. C.). The THF is evaporated. The residue is taken up in 40 ml of pentane. After centrifugation, the supernatant is removed and concentrated to isolate the crude ketene acetal after evaporation.

 The ketene acetals synthesized are characterized in IR by a band '((c = c) at 1680 cm -1.

III) Access to α-halocenes by halogenation of ketene acetals
5 mmol of crude ketene acetal are dissolved in 50 ml of dry THF and cooled to -70 ° C. 1.5 equivalents of halogenating agent (N-bromosuccinimide or N-chlorosuccinimide) in solid form are then added all at once by means of a bubble to solid. It is maintained at -70 ° C. for 1 hour, and 50 ml of a 0.4 M solution of sodium thiosulphate are then added at this temperature, and then the reaction medium is taken up in 80 ml of ether and washed with a solution of thiosulphate and then three times 50 ml of water. It is dried over MgSO 4. A filter is obtained, the residue is evaporated and the residue is analyzed by gas chromatography on HP1 column 25 m long (column B).

 The synthesized halogenated esters are characterized in IR by a Y (c = o) band at 1745 cm -1.

IV) Hydrolysis of the a-haloaenes esters
In a flask equipped with a condenser, the crude halogenated ester (5 mmol) in solution in 5 ml of acetone is placed.

20 ml of 20% hydrochloric acid solution (2.4N HCl) are added to this solution and the mixture is refluxed with acetone. The reaction is followed by
GIC (column A).

 When the reaction is complete (approximately 1 hour), the acetone is evaporated under vacuum and the aqueous phase is extracted with 3 times 40 ml of ether.

 The combined organic phases are evaporated and the residue is taken up in 20 ml of a 0.5M aqueous sodium hydroxide solution. The basic phase is washed with 3 times 40 ml of ether and then acidified with concentrated HCl to pH = 1. The acidic aqueous phase is extracted with 3 times 40 ml of ether, then the combined organic phases are dried over Na 2 SO 4 and evaporated. The crude residue is distilled under reduced pressure.

The halogenated acids synthesized are characterized in IR by a band
Y (c = o) to cm-1.

Examples to4:
In the different examples, one starts from an alkanoic acid
R - CH2 - COOH in which R represents a methyl radical (Example 1), an isopropyl radical (Example 2) and an isobutyl radical (Examples 3 and 4).

 The halogenating agent used is respectively N-chlorosuccinimide in Examples 1 to 3 and N-bromosuccinimide in Example 4.

The results obtained are recorded in the summary table:
Table I

<tb><SEP> u
<tb><SEP> ÉyOR * <SEP>> ÓH
<tb><SEP> O <SEP> O
<tb> N <SEP> Example <SEP> R <SEP> X <SEP> ed (%) <SEP> rdt (%) to <SEP> ee (%)
<tb><SEP> 1 <SEP> Me <SEP> Cl <SEP> 90 <SEP> 71 <SEP> 90
<tb><SEP> 2 <SEP> Pr <SEP> Cl <SEP> 96 <SEP> 70 <SEP> 95
<tb><SEP> 3 <SEP> iBu <SEP> Cl <SEP> 91 <SEP> 75 <SEP> 90
<tb><SEP> 4 <SEP> iBu <SEP> Br <SEP> 79 <SEP> 66 <SEP> 79
<tb> a) calculated with respect to the initial non-halogenated ester of formula:

Claims (18)

1 - Process for hydrolysis of a halogenated ester derived from a furanose derived from a sugar characterized in that it consists in hydrolyzing said ester with a mineral acid in a hydro-organic medium. 2- Process according to claim 1 characterized in that the mineral acid is hydrochloric acid, nitric acid, phosphoric acid, preferably hydrochloric acid. 3 - Process according to one of claims 1 and 2 characterized in that the normality of the aqueous solution of mineral acid used is less than 5 N and preferably between 1 and 3 N. 4- Process according to one of claims 1 to 3 characterized in that the amount of mineral acid used expressed by the ratio between the number of H + ions provided by the mineral acid and the number of moles of Engaged ester of formula (I) varies between 1 and 20, preferably between 2 and 10. 5 - Process according to one of claims 1 to 4 characterized in that the volume ratio between water and the organic solvent varies between 0.3 and 3.0. 6. Process according to one of claims 1 to 5 characterized in that the organic solvent is chosen from: - aliphatic alcohols such as ethanol, propanol, isopropanol, butanol, Isobutanol, hexanol, ethylene glycol, ketones such as acetone, diethylketone, methyl ethyl ketone, diacetone alcohol, 2,5-hexanedione. 7- Method according to one of claims 1 to 6 characterized in that the organic solvent is acetone or diacetone alcohol. 8- Method according to one of claims 1 to 7, characterized in that the concentration of the ester of formula (I) in the reaction solvent (water + organic solvent) varies between 0.01 and 2 moles / liter, preferably between 0.1 and 0.5 mole / liter. 9 - Process according to one of claims 1 to 8 characterized in that the temperature of the hydrolysis reaction is a temperature selected between 50'C and 100.0 and is preferably the reflux temperature of the reaction mixture. 10- Method according to one of claims 1 to 9, characterized in that the a-chiral halogenated ester corresponds to the following formula (I):

 in which the different symbols represent:  R represents a hydrocarbon radical having from 1 to 40 carbon atoms  which may be an aliphatic radical, saturated or unsaturated, linear or branched;  a cycloaliphatic radical, saturated, unsaturated or aromatic, monocyclic  or polycyclic; a cycloaliphatic or arylaliphatic radical, saturated or  unsaturated, linear or branched, a halogen atom, preferably an atom  fluorine, chlorine or bromine,  R * represents a radical derived from a tetrahydrofuranyl unit  X represents a halogen atom, preferably a chlorine atom or  bromine, different from R.  II - Process according to one of claims 1 to 10, characterized in that the a-chiral halogenated ester corresponds to formula (I) in which R represents an alkyl, alkenyl, alkadienyl, alkynyl, linear or branched radical having preferably from 1 to 24 carbon atoms: the hydrocarbon chain possibly being:  - interrupted by one of the following groups:

 in these formulas R5 represents hydrogen or a linear or branched alkyl radical having from 1 to 4 carbon atoms, preferably a methyl or ethyl radical,  and / or carrier of one of the following substituents:

 in these formulas1 R5 having the meaning given above. 12 - Process according to claim 11 characterized in that said radical R is carrying a cyclic substituent connected by a valency bond or by one of the following groups:

 in these formulas R5 having the meaning given above. 13- Method according to one of claims 1 to 12 characterized in that the a-chiral halogenated ester corresponds to formula (I) wherein R represents: - a linear or branched alkyl radical having 1 to 12 atoms of carbon, - a cycloalkylalkyl radical having, preferably, from 1 to 4 carbon atoms in the alkyl chain, - a phenylalkyl radical having, preferably, from 1 to 4 carbon atoms in the alkyl chain, - an optionally substituted cycloalkyl radical preferably having from 5 to 7 carbon atoms, an optionally substituted phenyl radical, an optionally substituted naphthyl radical. 14- Method according to one of claims 1 to 13, characterized in that the halogen-a-chiral ester corresponds to formula (I) wherein R represents: - the methyl, ethyl, propyl, isopropyl, n-butyl radical isobutyl, sec-butyl, tert-butyl, - cyclohexyl radical, - phenyl, tolyl, xylyl or naphthyl radicals optionally carrying linear or branched alkyl radicals having 1 to 4 carbon atoms or alkoxy radicals having from 1 to 4 carbon atoms, - the benzyl radical, phenylethyl. 15- Method according to one of claims 1 to 14 characterized in that the halogenated a-chiral ester corresponding to formula (I) wherein R represents a linear or branched alkyl radical having 1 to 12 carbon atoms and preferably from 1 to 4 carbon atoms. 16- Method according to one of claims 1 to 15, characterized in that the α-chiral halogenated ester corresponds to formula (I) in which R * represents a unit corresponding to the following formula (II):

 in said formula (II): R 1, R 2, which are identical or different, represent a linear or branched alkyl radical having from 1 to 12 carbon atoms, a cyclohexyl radical, a phenyl radical or a benzyl radical, R 3, R 4, which are identical; or different, represent a linear or branched alkyl radical having 1 to 12 carbon atoms, a cyclohexyl radical, a phenyl radical or a benzyl radical, - the radicals R1 and R2 on the one hand, and R3 and R4 on the other hand can together form a 5-membered (dioxolane) or 6-membered (1,4-dioxane) ring. 17- Method according to one of claims 1 to 16 characterized in that the a-chiral halogenated ester corresponds to the formula (I) wherein R * represents a furanose unit derived from the following sugars: glucose, allose , Altrose, mannose, galactose, talose, gulose, idose, ribose, arabinose, xylose and lyxose. 18- Method according to one of claims 1 to 17, characterized in that the α-chiral halogenated ester corresponds to formula (I) wherein R * represents the following radical:

 19- Method according to one of claims 1 to 18, characterized in that the a-chiral halogenated ester corresponding to formula (I) is an ester derived from a furanose unit bearing an OH in the 3-position and the one of the following halogenated alkanoic acids: - 2-chloropropionic acid - 2-bromo propionic acid - 2-chloro-butanoic acid - 2-bromo-butanoic acid - 2-chloro-3-methyl acid butanoic acid - 2-bromo-3-methylbutanoic acid - 2-chloro-3,3-dimethylbutanoic acid - 2-bromo 3,3-dimethylbutanoic acid - 2-chloro hexanoic acid - Acid 2-bromohexanoic acid - 2-chloro-4-methylpentanoic acid - 2-bromo-4-methylpentanoic acid 20 - Process according to one of claims 1 to 19, characterized in that the a-chiral halogenated ester which corresponds to formula (I) is an ester derived from a furanose unit bearing OH in the 3-position and one of the following halogenated alkanoic acids: 2-chloro-propionic acid - 2-chloro-3-methylbutanoic acid - 2-chloro-4-methylpentanoic acid - 2-bromo-4-methylpentanoic acid 21 - Process according to one of claims 1 to 20, characterized in that a-chiral halogenated ester corresponding to formula (I) is prepared by reaction with an N-halosuccinimide (N-bromosuccinimide or N-chlorosuccinimide) in an organic solvent, an O-silylated ketene acetal having the following formulas:

 in said formulas (III) or (III): - R * has the meaning given above in one of claims 10, 16 to 18, - the radicals R6, which may be identical or different, represent a linear or branched alkyl radical having from 1 to to 4 carbon atoms or a phenyl radical, preferably a methyl radical, - R has the meaning given above in one of claims 10 to 15. 22 - Use of the process of the invention described in claims 1 to 21 to the preparation of (S) -2-chloropropionic acid.