WO2020152200A1

WO2020152200A1 - Process for preparation of heteroarylketones

Info

Publication number: WO2020152200A1
Application number: PCT/EP2020/051465
Authority: WO
Inventors: Swapnil Yerande; Harish SHINDE; Vishal BHOR; Prashant KAPSE; Roland Goetz
Original assignee: Basf Se
Priority date: 2019-01-25
Filing date: 2020-01-22
Publication date: 2020-07-30
Also published as: AR117876A1

Abstract

The present invention relates to a process for preparation of heteroarylketones of formula (I). The invention relates to an efficient process for the preparation of heteroarylketones for formula (I) which find use as herbicides. (I)

Description

PROCESS FOR THE PREPARATION OF HETEROARYLKETONES FIELD OF THE INVENTION The present invention relates to a process for the preparation of heteroarylketones of the formula (I). The invention relates to an efficient process for the preparation of heteroarylketones of the formula (I) which are used as herbicides.

BACKGROUND OF THE INVENTION Heteroarylketones of formula (I) are described in WO96/26206 and WO98/31681. The heteroarylketones of formula (I) are directed to an herbicidal compound 4-[3-(4,5-dihydro- 1,2-oxazol-3-yl)-2-methyl-4-methylsulfonylbenzoyl]-2-methyl-1H-pyrazol-3-one or [3-(4,5- dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-(5-hydroxy-1-methyl-pyrazol-4- yl)methanone. WO 96/26206 discloses a process for preparing 4-(3-(4,5-dihydroisoxazol-3-yl) benzoyl)-5- hydroxypyrazoles where, in the last step, a 5-hydroxypyrazole is reacted with a 3-(4,5- dihydroisoxazol-3-yl) benzoic acid derivative. The 3-(4,5-dihydroisoxazol-3-yl) benzoic acid derivative required for this process can only be obtained with difficulty, via several steps. Accordingly, the process is relatively expensive and not optimal economically. DE 19709118 describes a process for preparing 3-(4,5-dihydroisoxazol-3-yl) benzoic acids starting from 3-bromo-(4,5-dihydroisoxazol-3-yl) benzene, Grignard reagents and carbon dioxide. WO 99/58509 describes a process for preparing 3-heterocyclyl-substituted benzoyl derivatives with reduced steps. However, the yields obtained by the process are not satisfactory.

The known prior art describe processes to synthesize 4-[3-(4,5-dihydro-1,2-oxazol-3-yl)-2- methyl-4-methylsulfonylbenzoyl]-2-methyl-1H-pyrazol-3-one from a compound of formula (III). However, there are several disadvantages in terms of reaction conditions, the yields and/or work-up requirements rendering them unsuitable for industrial scale production. Another disadvantage of the processes described in the prior art is the formation of impurities which lead to further reduction of the yield. An object of the presently claimed invention is to provide an improved process for the synthesis of heteroaryl ketones that have herbicidal activity. Furthermore, the object underlying the presently claimed invention is to optimize the synthesis of heteroarylketones of formula (I). The present invention includes several advantages, for example, a more efficient process having minimal waste throughput and waste treatment. The presently claimed process is shown to avoid the need for carefully controlled reaction conditions, tedious multiple purification techniques, and the use of stoichiometric amounts of organometallic reagents. Description This object is achieved by the processes described in detail hereafter. A first aspect of the present invention relates to a process for the preparation of a compound of the general formula (I) or its salts as describes in step (A). Step (A): The process for the preparation of a compound of the general formula (I) or its salts

wherein

R1 is C₁-C₄ alkyl, R² is Cl or C₁-C₄ alkyl, ³ is hydrogen or C₁-C₄ alkyl and ⁴ is C₁-C₄ alkyl, comprising at least the step of reacting a compound of formula (II),

wherein

R1 is C₁-C₄ alkyl and M is H or an alkali metal atom with a compound of formula

wherein

X is Cl, Br, I, S(=O)₂-CH₃ or S(=O)₂-CF₃, R² is Cl or C₁-C₄ alkyl, R3 is hydrogen or C₁-C₄ alkyl, and R⁴ is C₁-C₄ alkyl, in the presence of carbon monoxide, at least one alkali metal iodide, at least one base, at least one metal catalyst and at least one phosphine compound. Step B: Further, the compound of general formula (III) is obtained by one or more of the following steps: a) reacting a nitro-methylphenyl compound of formula IV,

wherein R₂ is Cl or C₁-C₄ alkyl, with an organic nitrile of the formula R⁵ -ONO, wherein R⁵ is n-butyl, in the presence of at least one base to give and oxime of the formula (V),

wherein R² is Cl or C₁-C₄ alkyl, a) cyclization of the oxime of the formula (V) with an alkene of the formula (VI),

wherein R6, R7, R8 are, identical or different, hydrogen or C₁-C₄ alkyl, in the presence of at least one base to give a compound of formula (VII),

wherein R² is Cl or C₁-C₄ alkyl and R3 is hydrogen or C₁-C₄ alkyl, b) reducing the compound of formula (VII) in the presence of at least one catalyst to give the compound of formula (VIII),

wherein R² is Cl or C₁-C₄ alkyl, and R3 is hydrogen or C₁-C₄ alkyl, c) substituting the para amino position in the compound of formula (VIII) to give the compound of formula (IX),

wherein R² is Cl or C₁-C₄ alkyl, R3 is hydrogen or C₁-C₄ alkyl and X is Cl, Br, I, S(=O)₂-CH₃ or S(=O)₂-CF₃; d) reacting the compound of formula (IX) with a dialkyl disulfide of formula (X)

wherein R4 is C₁-C₄ alkyl,

in the presence of an organic nitrile of the formula R5-ONO, wherein R5 is n-butyl, and at least one catalyst to give the compound of formula (XI),

wherein R² is Cl or C₁-C₄ alkyl, R³ is hydrogen or C₁-C₄ alkyl, R⁴ is C₁-C₄ alkyl, and X is Cl, Br, I, S(=O)₂-CH₃ or S(=O)₂-CF₃ e) oxidizing the compound of formula (XI) with at least one oxidizing agent to obtain the compound of formula (III),

wherein X is Cl, Br, I, S(=O)₂-CH₃ or S(=O)₂-CF₃, R² is Cl or C₁-C₄ alkyl, R³ is hydrogen or C1- C4 alkyl, and R⁴ is C₁-C₄ alkyl, Salts of the compounds according to the invention can be formed in a customary manner, for example, by reacting the compound with an acid of the anion in question, if the compounds according to the invention have a basic functionality or by reacting acidic compounds according to the invention with a suitable base. Salts of the compounds prepared according to the invention are preferably agriculturally acceptable salts. The organic moieties or groups mentioned in the above definitions of the variables are - like the term halogen - collective terms for individual listings of the individual group members. The term "C_v-C_w" indicates the number of carbon atom possible in each case. The term "halogen" refers to flouro, chloro, bromo and iodo. The term "C₁-C₄-alkyl" refers to a straight-chained or branched saturated hydrocarbon group having 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, 1-methylethyl, butyl, 1- methylpropyl, 2-methylpropyl, 1,1-dimethylethyl. The term“substituted” if not specified otherwise refers to substituted with 1, 2 or maximum possible number of substituents. If substituents are more than one, then they are independently from each other are same or different, if not mentioned otherwise.

Meanings of the terms that are not defined herein are generally known to a person skilled in the art or in the literature. Preferred embodiments of the present invention are described below. Step (A) of the present invention for the preparation of a compound of the general formula (I) or its salts is as follows: Reacting a compound of formula (II), wherein

R¹ is C₁-C₄ alkyl and M is H or an alkali metal atom with a compound of formula (III),

wherein

X is Cl, Br, I, S(=O) ² 3

2-CH₃ or S(=O)₂-CF₃, R is Cl or C₁-C₄ alkyl, R is hydrogen or C₁-C₄ alkyl, and R4 is C₁-C₄ alkyl, in the presence of carbon monoxide, at least one alkali metal iodide, at least one base, at least one metal catalyst and at least one phosphine compound to obtain a compound of formula (I)

wherein

R¹ is C₁-C₄ alkyl, R² is Cl or C₁-C₄ alkyl, R³ is hydrogen or C₁-C₄ alkyl and R4 is C₁-C₄ alkyl. I n an embodiment, of the present invention R¹ is C_!_C₂ alkyl, R² is C₁--C₄ alkyl, R³ is hydrogen or C₁--C₄ alkyl, R⁴ is C1-C4 alkyl.

In another embodiment, of the present invention R¹ is methyl, R² is C₁--C₂ alkyl, R³ is hydrogen or C₁-C₄ alkyl and R⁴ is C₁-C₄ alkyl.

In another embodiment, of the present invention R¹ is methyl, R² is methyl, R³ is hydrogen or C₁-C₄ alkyl and R⁴ is C₁-C₄ alkyl.

In another embodiment, of the present invention R¹ is methyl, R² is methyl, R³ is hydrogen and R⁴ is C₁-C₄ alkyl.

In yet another embodiment, of the present invention R¹ is methyl, R² is methyl, R³ is hydrogen and R⁴ is C₁--C₂ alkyl.

I n another embodiment, of the present invention R¹ is methyl, R² is methyl, R³ is methyl and R⁴ is methyl.

In a preferred embodiment, of the present invention R¹ is methyl, R² is methyl, R³ is hydrogen and R⁴ is methyl.

The temperatures and the duration times of the reactions may be varied in broad ranges, which the person skilled in the art knows from analogous reactions. The temperatures often depend on the reflux temperature of the solvents or at higher temperature under pressure. The end of the reaction can be monitored by methods known to a person skilled in the art, for example, thin layer chromatography or H PLC or GC.

I n an embodiment, the mass ratio of reactant to solvent is in the range of 1: 5 to 1: 20,

In another embodiment, the mass ratio of reactant to solvent is in the range of 1:6 to 1:10.

If not otherwise indicated, the reactants can in principle be contacted with one another in any desired sequence.

The person skilled in the art also knows the best work-up of the reaction mixture after the end of the reaction.

In the present invention, step (A) takes place in the presence of at least one alkali metal iodide, at least one base, at least one metal catalyst and at least one phosphine compound and at least one solvent, wherein the at least one metal is preferably in a form of a free state of formula M or in a form of a metal complex of formula M(L)_n

In the following, preferred embodiments regarding step (A) of the invention are provided. It is to be understood that the preferred embodiments mentioned above and those still to be illustrated below of step (A) of the invention are to be understood as preferred alone or in combination with each other.

In one embodiment, the at least one alkali metal iodide is selected from the group consisting of sodium iodide, potassium iodide, lithium iodide. In a preferred embodiment, the at least one alkali metal iodide is sodium iodide. In one embodiment, the at least one metal (M) is selected from the group consisting of nickel (Ni), cobalt (Co), iron (Fe), ruthenium (Ru), rhodium (Rh), palladium (Pd), iridium (Ir), platinum (Pt), silver (Ag), copper (Cu), zinc (Zn), molybdenum (Mo) and tungsten (W). In preferred embodiment, the at least one metal (M) is selected from the group consisting of palladium (Pd), nickel (Ni), copper (Cu) and iron (Fe). In one embodiment, L, identical or different, is Cl, Br, I, P(C₅-C₁₄-aryl)_m, P(C₅-C₁₂-heteroaryl)_m, P(C₅-C₁₂-heteroaryl)_m(C₅-C₁₄-aryl)_3-m, CN, C₁-C₆-alkyl, C₁-C₆-alkyl-O-C₁-C₆-alkyl, -O-CO-C₁- C₆-alkyl, OH, nitro, -O-C₁-C₆-alkyl, C₁-C₄-haloalkoxy, C₃-C₈-cycloalkyl, C₃-C₈-halocycloalkyl, C₃-C₈-cycloalkenyl, C₅-C₁₄-aryl, C₅-C₁₄-aryl-(CH₂)_o-(Q)_p-(CH₂)_o-C₅-C₁₄-aryl and 1,1ʼ- bis(diphenyl phosphino)ferrocene ; whereby Q represents a bridging group selected from the group consisting of -CR8R9, -O-, -S-, -NR10R¹1, -SiR¹²R¹³ and -CO-, wherein R8 and R9, identical or different, are hydrogen, C₁-C₁₂ alkyl, C₅-C₁₄-aryl or C₅-C₁₂-heteroaryl; wherein R¹⁰, R¹¹, R¹² and R¹³, identical or different, are hydrogen or C₁-C₄ alkyl or R10 together with R¹¹ forms C₅- C₁₂-membered heterocycloalkyl, C₅-C₁₂-membered heterocycloalkenyl or C₅-C₁₂-membered heteroaryl and L is unsubstituted or further substituted by 1, 2, 3, 4 or 5 identical or different groups selected from the group consisting of Cl; F; Br; I; CN; -NO₂; -NR¹⁰R¹¹, -P(phenyl)₂, - OH, unsubstituted or substituted C₁-C₁₂-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, unsubstituted or substituted C₅-C₁₄-aryl, unsubstituted or substituted C₅-C₁₂-heteroaryl, C₅-C₁₂-membered heterocycloalkyl, C₅-C₁₂ ²-mmbered heterocycloalkenyl, -O-(CCH₂r₂)r_r-O-, -_C(=O)¹⁴, -C(=O)-O- R15

, -C=N-R¹⁶, SO₃H, -O-C₁-C₆-alkyl and -O-Si-C₁-C₄-alkyl; wherein

R14 is hydrogen or C₁-C₄-alkyl;

R15 is hydrogen or C₁-C₄-alkyl;

R16 is hydrogen, C₁-C₁₂-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₅-C₁₄-aryl, C₅-C₁₂-heteroaryl or C₃-C₁₂-cycloalkyl;

n is 0,1,2,3,4,5 or 6

m is 1,2 or 3;

o is 0,1 or 2

p is 0,1 or 2 and

r is 1,2,3,4 or 5. In yet another embodiment, L is, identical or different, Cl, Br, I, P(C₅-C₁₄-aryl)_m, CN, unsubstituted or substituted C₁-C₁₂-alkyl, C₁-C₄-alkoxy, C₃-C₈-cycloalkenyl, -O-CO-C₁-C₆- alkyl, C₅-C₁₄-aryl, 1,1ʼ- bis(diphenyl phosphino)ferrocene and C₅-C₁₄-aryl-(CH₂)_o-(Q)_p-(CH₂)_o- C₅-C₁₄-aryl;

wherein

m is 1,2 or 3;

o is 0,1 or 2

p is 0,1 or 2. In more preferred embodiment, L is, identical or different, Cl, -OCOCH₃, P(phenyl)₃, P(o- tolyl)₃, CN, dibenzylidene acetone, -CH₃CN, 1,5-cyclooctadiene or 1,1ʼ- bis(diphenyl phosphino) ferrocene. In another embodiment, Ln is supported on silica gel, dendrimers, polystyrenes or mesoporous siliceous foam, for example as described in Vivek et. al., Tetrahedron, 63, 2007, 6949-6976. In another embodiment, R⁸ is hydrogen, C₁-C₁₂ alkyl, C₅-C₁₄-aryl or C₅-C₁₂-heteroaryl.

In another embodiment, R⁸ is hydrogen, methyl or ethyl.

In another embodiment, R⁹ is hydrogen, C₁-C₁₂ alkyl, C₅-C₁₄-aryl or C₅-C₁₂-heteroaryl.

In more preferred embodiment, R⁹ is hydrogen.

In another embodiment, R¹⁰ is hydrogen, methyl, ethyl, propyl or n-butyl.

In another embodiment, R₁ ¹ is hydrogen, methyl, ethyl, propyl or butyl.

In another embodiment, R₁₂ is hydrogen, methyl, ethyl, propyl or butyl.

In another embodiment, R¹³ is hydrogen, methyl, ethyl, propyl or butyl.

In another preferred embodiment, R¹³ is hydrogen, methyl or ethyl.

In yet another embodiment, R10 together with R11 forms C₅-C₁₂-membered heterocycloalkyl, C₅-C₁₂-membered heterocycloalkenyl or C₅-C₁₂-membered heteroaryl.

In another embodiment, R¹⁴ is hydrogen or C₁-C₄-alkyl.

In yet another embodiment, R14 is hydrogen, methyl, ethyl, propyl or butyl.

In another embodiment, R¹⁵ is hydrogen, methyl, ethyl, propyl or butyl.

In another embodiment, R16is hydrogen, C₁-C₁₂-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₅-C₁₄-aryl, C₅-C₁₂-heteroaryl or C₃-C₁₂-cycloalkyl.

In another embodiment, n is 0,1,2,3,4,5 or 6.

In yet another preferred embodiment, n is 0,1 or 2.

In yet another preferred embodiment, n is 3,4,5 or 6.

In more preferred embodiment, n is 2, 3 or 4.

In another embodiment, m is 1, 2 or 3.

In another embodiment, o is 0,1 or 2

In another embodiment, p is 0,1 or 2 and

In another embodiment, r is 1,2,3,4 or 5.

In more preferred embodiment, M, L and n are as follows in Table 1: Table 1

The amount of at least one M and/or MLn is in the ratio of 1: 100 mole to 1:500 mole of the compound of formula (III).

In a preferred embodiment the amount of at least one M and/or MLn is in the ratio of 1: 150 mole to 1:400 mole of the compound of formula (III)

In a preferred embodiment, the at least one metal catalyst is in a free state of palladium such as Pd/C.

In a preferred embodiment, the at least one metal catalyst is in a form of a metal complex selected from the group consisting of Pd(OCOCH₃)₂ and Pd(CI)₂.

In one embodiment, the phosphine compound is PX₁X₂X₃ or (PX₁X₂)₂(B)_q, whereby X₁, X₂and X₃, identical or different, are F, Cl, Br, I, -NR¹⁷R¹⁸ hydrogen, -0-C₁-C₆-alkyl, -0-CO-C₁-C₆-alkyl, -C₁₂-alkyl, C₂-C₆-alkenyl, C₂-C₆-al kyny I, C₅-C₁₄-aryl, C₅-C₁₂-heteroaryl, C₃-C₁₂-cycloalkyl, C₃- C₁₂-cycloalkenyl, C₃-C₁₂-heterocycloalkyl, C₃-C₁₂-heterocycloalkenyl or -Si-(C₁--C₁₂-alkyl)₃, whereby B is CR¹⁹R²⁰, -0-, -phenyl-O-phenyl-, -S-, -NR¹⁷R¹⁸, -Si R²¹R²² or -C(=O)-, wherein R¹⁹ and R²⁰, identical or different, are hydrogen, C₁-C₁₂-a I ky I , C₅-C₁₄-aryl or C₅-C₁₂-heteroaryl, wherein R¹⁷, R¹⁸, R²¹ and R²², identical or different, are hydrogen or C₁--C₄-alkyl or R¹⁷ together with Reforms heterocycloalkyl, heterocycloalkenyl or C₅-C₁₂-heteroaryl; whereby X₄, X₂and X₃ , identical or different, are unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or different groups selected from the group consisting of Cl; F; Br; I; CN; -N0₂; -NR¹⁷R¹⁸, -P(phenyl)₂, - OH, unsubstituted or substituted C₁--C₁₂-aI kyI , C₂-C₆-alkenyl, C₂-C₆-a I kyny I , unsubstituted or substituted C₅-C₁₄-aryl, unsubstituted or substituted C₅-C₁₂-heteroaryl, -0-(CH₂)_r-0-, - C(=O)R²³_ -C(=O)-O-R²⁴ -C=N-R²⁵, -S0₃H, -O-C₁-C₆-alkyl and -O-Si- C₁-C.₄-alkyl, C₅-C₁₂- membered heterocycloalkyl, C₅-C₁₂-membered heterocycloalkenyl and C₅-C₁₂-heteroaryl; wherein q is 1,2, 3, 4, 5 or 6;

r is 1,2, 3, 4 or 5;

R²³ is hydrogen or C₄-C₄-a I ky I ;

R²⁴ is hydrogen or C₄-C₄-a I ky I ; and

R²⁵ is hydrogen, C₁--C₁₂-a I ky I , C₂-C₆-alkenyl, C₂-C₆-a I kyny I , C₅-C₁₄-aryl, C₅-C₁₂-heteroaryl or C₃- C₁₂-cycloalkyl;

or their acceptable salts thereof.

In another embodiment, X₄, X₂and X₃, identical or different, are C₁--C₁₂-a I kyl , C₅-C₁₄-aryl or C₅- C₁₂-heteroaryl.

In more preferred embodiment, X₄, X₂and X₃, identical or different, are 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, 1,1- dimethylpropyl, 1,2-dimethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4- methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3- d i methyl butyl , 3,3-dimethylbutyl, 1-ethyl butyl, 2-ethyl butyl, 1,1,2-trimethyl propyl, 1,2,2- trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl, n-octyl, 1-methylpropyl, 2-methylheptyl or 1,1-dimethylethyl. In yet another preferred embodiment, X₁, X₂ and X₃, identical or different, are phenyl or naphthyl. In yet another preferred embodiment, X₁, X₂ and X₃, identical or different, are pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazinyl, thienyl, furanyl, pyrrolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolyl, triazolyl, thiadiazolyl, oxadiazolyl, and tetrazolyl rings, and the fused bicyclic moieties formed by fusing one of these monocyclic groups with a phenyl ring or with any of the heteroaromatic monocyclic groups to form a C₈-C₁₀ bicyclic group such as indolyl, benzimidazolyl, indazolyl, benzotriazolyl, isoquinolinyl, quinolinyl, benzothiazolyl, benzofuranyl, benzothienyl, benzisoxazolyl, pyrazolopyridyl, quinazolinyl, quinoxalinyl or cinnolinyl. In another embodiment, R17 is hydrogen or C₁-C₄ alkyl.

In another embodiment, R17 is hydrogen, methyl, ethyl, propyl or butyl.

In another embodiment, R18 is hydrogen, methyl, ethyl, propyl or butyl.

In another preferred embodiment, R18 is hydrogen.

In yet another embodiment, R17 together with R18 forms C₅-C₁₂-membered heterocycloalkyl, C₅-C₁₄-membered heterocycloalkenyl or C₅-C₁₂-heteroaryl.

In another embodiment, R19 is hydrogen, C₁-C₁₂-alkyl, C₅-C₁₄-aryl or C₅-C₁₂-heteroaryl.

In yet another embodiment, R19 is hydrogen, methyl ethyl, propyl, phenyl or naphthyl.

In another embodiment, R20 is hydrogen, C₁-C₁₂-alkyl, C₅-C₁₄-aryl or C₅-C₁₂-heteroaryl.

In yet another embodiment, R20 is hydrogen, methyl ethyl, propyl or butyl.

In another embodiment, R21 is hydrogen or C₁-C₄ alkyl.

In another preferred embodiment, R21 is hydrogen.

In another embodiment, R22 is hydrogen, methyl, ethyl, propyl or butyl.

In yet another embodiment, R22 is hydrogen, methyl or ethyl.

In another embodiment, R23 is hydrogen or C₁-C₄-alkyl.

In another preferred embodiment, R23 is hydrogen, methyl, ethyl, propyl or butyl.

In another embodiment, R24 is hydrogen methyl, ethyl, propyl or butyl. In another embodiment, the at least one phosphine compound is selected from the group consisting of allyldiphenylphosphine; 1,3-bis(diphenylphosphino)propane; 1,3-bis(dicyclo- hexylphosphino)propane, 1,4-bis(diphenylphosphino)butane, di-tert-butyl(phenyl)phos- phine, tri-tert-butylphosphine ,di-tert-butyl(phenyl)phosphine tetrafluoroborate; (2-am- monioethyl) di-tert-butylphosphonium bis(tetrafluoroborate); (2-ammonioethyl) diiso- propylphosphonium bis(tetrafluoroborate); (3-ammoniopropyl) di-tert-butylphosphonium bis(tetrafluoroborate); (3-ammoniopropyl) diisopropylphosphonium bis(tetrafluoroborate); bis(3,5-bis(trifluoromethyl)phenyl)(2¢,6¢-bis(isopropoxy)-3,6-dimethoxybiphenyl-2- yl)phosphine; benzyldiphenylphosphine; (2-biphenyl)di-1-adamantylphosphine; 1-[2- [bis(tert-butyl)phosphino]phenyl]-3,5-diphenyl-1H-pyrazole; bis[2-(diadaman- tylphosphino)ethyl]amine; 2-[bis(3,5-di-tert-butyl-4- methoxyphenyl)phosphino]benzaldehyde; 2,6-bis(di-tert-butylphosphinomethyl)pyridine; bis(dicyclohexylphosphinophenyl)ether; bis(diethylamino)phenylphosphine;

bis(dimethylamino)chlorophosphine; 2-[bis(3,5-dimethylphenyl)phosphino]benzaldehyde; bis[4-(3,3,4,4,5,5,5-heptafluoro-2,2-bis(trifluoromethyl)pentyl)phenyl]phenylphosphine; bis(2-methoxyphenyl)phosphine; bis[4-(1H,1H,2H,2H- perfluorodecyl)phenyl]phenylphosphine; 1,1¢-bis(phenylphosphinidene)ferrocene; (2- bromophenyl)dicyclohexylphosphine; (2-bromophenyl)diphenylphosphine; tert- butyldicyclohexylphosphine; tert-butyldicyclohexylphosphonium tetrafluoroborate; tert- butyldiisopropylphosphine; tert-butyldiphenylphosphine; 1-(dicyclohexylphosphino)-2,2- Diphenyl-1-methylcyclopropane; cyclohexyldiphenylphosphine; di(1-adamantyl)-2- dimethylaminophenylphosphine; di-1-adamantylphosphine; di(1-adamantyl)-(2- triisopropylsiloxyphenyl)phosphine; (5H-dibenzo[a,d]cyclohepten-5-yl)diphenylphosphine; di-tert-butylcyclohexylphosphine; di-tert-butyl N,N-diisopropylphosphoramidite; di-tert- butylmethylphosphine; di-tert-butyl(methyl)phosphonium tetrafluoroborate; di-tert- butyl(methyl)phosphonium tetrafluoroborate; di-tert-butylneopentylphosphine; di-tert- butylneopentylphosphonium tetrafluoroborate; di-tert-butylphenylphosphine; di-tert- butylphosphate potassium salt; 2¢-(di-tert-butylphosphino)acetophenone ethylene ketal; 2-(di-tert-butylphosphino)dimethylaminobenzene; 2-(di-tert-butylphosphino)ethylamine; 2- ((di-tert-butylphosphinomethyl)-6-diethylaminomethyl)pyridine; 5-(di-tert-butylphosphino)- 1-(naphthalen-1-yl)-1H-pyrazole; 5-(di-tert-butylphosphino)-1¢, 3¢, 5¢-triphenyl-1¢H- [1,4¢]bipyrazole; 3-(di-tert-butylphosphonium)propane sulfonate; P,P- dichloroferrocenylphosphine; dicyclohexyl-(2,6-diisopropylphenyl)phosphine;

dicyclohexyl(4-(N,N-dimethylamino)phenyl)phosphine; dicyclohexyl(ethyl)phosphine;

dicyclohexyl(4-isopropylphenyl)phosphine; dicyclohexyl(2-methylphenyl)phosphine;

dicyclohexylphenylphosphine; 2¢-(dicyclohexylphosphino)acetophenone ethylene ketal; 2- (dicyclohexylphosphino)benzophenone; 2-(dicyclohexylphosphino)-N,N-diisopropyl-1H- indole-1-carboxamide; N -(dicyclohexyl phosphino)-2-(2¢-methoxyphenyl)indole; 2- [(dicyclohexylphosphino)methyl]-1,3-bis(2,6-diisopropylphenyl)-4,5-dimethylimidazolium iodide; 2-(2-dicyclohexylphosphinophenyl)-1,3-dioxolane; 2-[2- (dicyclohexylphosphino)phenyl]-N-methylindole; dicyclohexyl(2,4,6- trimethylphenyl)phosphine; diethylphenylphosphine; diethylphosphine; 4- (diethylphosphino)-N,N-dimethylaniline; 9-[2-(diisopropylphosphino)phenyl]-9H-carbazole; 2-[di(2-methoxyphenyl)phosphino]benzenesulfonic acid;

dimethylaminophenylchlorophosphine; 4-(dimethylamino)phenyldiphenylphosphine; 2-(1,1- dimethylpropyl)-6-(diphenylphosphino)pyridine; diphenyl(2-methoxyphenyl)phosphine; 4- diphenylphosphanylbenzoic acid; 2-(diphenylphosphino)benzaldehyde; 2- (diphenylphosphino)benzaldehyde oxime; 3-(diphenylphosphino)benzenesulfonic acid sodium salt; 2-(diphenylphosphino)benzoic acid; 4-(diphenylphosphino)benzoic acid; N-[2- (diphenylphosphino)benzylidene] cyclohexylamine; 2-(diphenylphosphino)-N,N- dimethylbenzylamine; 2-(diphenylphosphino)ethanaminium tetrafluoroborate; 2- (diphenylphosphino)ethylamine; 2-(2-(diphenylphosphino)ethyl)pyridine; 3- (diphenylphosphino)propan-1-aminium tetrafluoroborate; 3-(diphenylphosphino)-1- propylamine; 4-(diphenylphosphino) styrene; 2-(diphenylphosphino)-N,N,N- trimethylbenzylammonium triflate;diphenyl-2-pyridylphosphine; diphenyl(o-tolyl)phosphine; diphenyl(p-tolyl)phosphine; diphenylvinylphosphine; 2-(di-p-tolylphosphino)benzaldehyde; ethyldiphenylphosphine; [4-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10- heptadecafluorodecyl)phenyl] diphenylphosphine; (4-hydroxyphenyl)diphenylphosphine; isopropyldiphenylphosphine; 1-methyl-2-(2-dicyclohexylphosphinophenyl)-1H- benzoimidazole; 1-methyl-2-(2-diisopropylphosphinophenyl)-1H-benzoimidazole;

methyldiphenylphosphine; 1-methyl-2-(2-diphenylphosphinophenyl)-1H-benzoimidazole; 1,2,3,4,5-pentaphenyl-1¢-(di-tert-butylphosphino)ferrocene; phenylbis[4- (3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)phenyl]phosphine; phenyldi(o-tolyl)phosphine; phenylphosphine; 4,4¢-(phenylphosphinidene)bis(benzenesulfonic acid) dipotassium salt hydrate; tetrapropylphosphonium bromide; triallylphosphine; tribenzylphosphine;

tributylphosphine; tri-n-butylphosphine; tri-tert-butylphosphine; tri-tert-butylphosphine; tri- tert-butylphosphine; tributylphosphine tetrafluoroborate; tri-tert-butylphosphonium tetrafluoroborate; tricyclohexylphosphine; tricyclohexylphosphine; tricyclohexylphosphine; tricyclohexylphosphine tetrafluoroborate; tricyclopentylphosphine; tricyclopentylphosphine tetrafluoroborate; triethylphosphine; triethylphosphine; ((4-trifluoromethyl)phenyl)di-tert- butylphosphine, tri(2-furyl)phosphine; ((2,4,6-tri-isopropyl)phenyl)di-cyclohexylphosphine; triisopropylphosphine; triisopropylphosphonium tetrafluoroborate; trimethylphosphine;

trimethylphosphonium tetrafluoroborate; tri-1-naphthylphosphine; trioctylphosphine;

triphenylphosphine; triphenylphosphine hydrobromide; 4-(triphenylphosphonio)butane-1- sulfonate; tripropylphosphine; tris[3,5-bis(trifluoromethyl)phenyl]phosphine; tris(4- chlorophenyl)phosphine; tris(diethylamino)phosphine; tris(2,6-dimethoxyphenyl)phosphine; tris(dimethylamino)phosphine; tris(3,5-dimethylphenyl)phosphine; tris(2,4-dimethyl-5- sulfanatophenyl)phosphine trisodium salt; tris[2-(diphenylphosphino)ethyl]phosphine;

tris(4-fluorophenyl)phosphine; tris[4-(heptadecafluorooctyl)phenyl]phosphine;

tris(hydroxymethyl)phosphine; tris(4-methoxy-3,5-dimethylphenyl)phosphine; tris(o- methoxyphenyl)phosphine; tris(4-methoxyphenyl)phosphine; tris(4-methyl-1- piperazinyl)phosphine; tris(pentafluorophenyl)phosphine; tris(1-pyrrolidinyl)phosphine; tris[4-(tridecafluorohexyl)phenyl]phosphine; tris[4-(3,3,4,4,5,5,6,6,7,7,8,8,8- tridecafluorooctyl)phenyl]phosphine; tris(4-trifluoromethylphenyl)phosphine; tris(2,4,6- trimethoxyphenyl)phosphine; tris(2,4,6-trimethylphenyl)phosphine;

tris(trimethylsilyl)phosphine; tri(o-tolyl)phosphine; tri(p-tolyl)phosphine; tri-o- tolylphosphine tetrafluoroborate; and 2-(dicyclohexylphosphino)-3,6-dimethoxy- 2¢,4¢,6¢-triisopropyl-1,1¢-biphenyl or acceptable salts thereof. In another preferred embodiment, the at least one phosphine compound is selected from the group consisting of triphenylphosphine, 1,3-bis(dicyclohexylphosphino)propane, 1,4- bis(diphenylphosphino)butane, di-tert-butyl(phenyl)phosphine and tri-tert-butylphosphine. In an embodiment, the mole ratio of at least one phosphine compound to the at least one metal catalyst is in the range of 1:0.010 to 1:0.20

In another embodiment, the mole ratio of at least one phosphine compound to the at least one metal catalyst is in the range of 1:0.025 to1:0.175.

In a most preferred embodiment, the mole ratio of the at least phosphine compound to the at least one metal catalyst is in the range of 1:0.05 to1:0.160 In a most preferred embodiment, the mole ratio of the at least phosphine compound to the at least one metal catalyst is in the range of 1:0.075 to 1:0.15.

In an embodiment, reaction temperature of the step (A) is kept within a range of from 50oC to 150°C, preferably in the range of from 50°C to 130°C, more preferably in the range of from 55°C to 120°C.

In an embodiment, the reaction of the step (A) is carried out at of pressure of 5 bar to 20 bar, preferably in the range of from 7 bar to 15 bar, more preferably in the range of 9 bar to 15 bar. In an embodiment, the at least one solvent of step (A) is selected from the group consisting of esters, ethers, aromatic hydrocarbons and acetals. In one embodiment, the solvent of step (A) is triethylorthoformate, trimethylorthoformate, tripropylorthoformate, tributylorthoformate, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4- dioxane, diethyl ether, diisopropyl ether, di-n-propyl ether, di-n-butyl ether, methyl-tert-butyl ether, diisobutyl ether, tetrahydropyran, dimethoxymethane, dimethoxypropane, dimethoxybutane, toluene, xylene, cyclohexane and monochlorobenzene. In an embodiment, the at least one base in step (A) is selected from organic bases or inorganic bases. In an embodiment, the organic bases are selected from the group consisting of N(R27)₃, N- methyl piperidine, N-methyl pyrrolidine, N-methyl morpholine, piperidine, dimethyl amino pyridine, pyridine, lithium hexamethyldisilazide, sodium hexamethyldisilazide and tetra-C₁- C₆-alkyl ammonium hydroxide, wherein R27 is, identical or different, hydrogen, C₁-C₆-alkyl, C₅- C₁₄-aryl, or C₃-C₆-cycloalkyl. In an embodiment, the inorganic bases are selected from the group consisting of alkali metal hydroxide, alkaline earth hydroxide, alkali metal bicarbonate, alkaline earth bicarbonate, alkali metal carbonate, alkaline earth carbonate, alkali metal phosphate, alkali metal alkoxide and alkaline earth alkoxide. In another embodiment,the alkali metal hydroxide is selected from group consisting of lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide and cesium hydroxide; the alkaline earth hydroxide is selected from the group consisting of magnesium hydroxide, calcium hydroxide, strontium hydroxide and barium hydroxide; the alkali metal bicarbonate is selected from the group consisting of lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, rubidium bicarbonate and cesium bicarbonate; the alkaline earth bicarbonate is selected from the group consisting of magnesium bicarbonate, calcium bicarbonate, strontium bicarbonate and barium bicarbonate; the alkali metal carbonate is selected from the group consisting of lithium carbonate, sodium carbonate, potassium carbonate, rubidium carbonate and cesium carbonate; the alkaline earth carbonate is selected from group the consisting of magnesium carbonate, calcium carbonate, strontium carbonate and barium carbonate; the alkali metal phosphate is selected from the group consisting of monosodium phosphate, disodium phosphate, trisodium phosphate, monopotassium phosphate, dipotassium phosphate and tripotassium phosphate; the alkali metal alkoxide is selected from the group consisting of NaOR28, KOR28, RbOR28 and CsOR28; the alkaline earth alkoxide is selected from the group consisting of Mg(OR28)₂, Ca(OR28)₂ and Ba(OR28)₂; wherein R28 is, identical or different, C₁-C₄-alkyl. In a preferred embodiment, the at least one inorganic base is selected from the group consisting of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, monosodium phosphate, disodium phosphate, trisodium phosphate, monopotassium phosphate, dipotassium phosphate and tripotassium phosphate. In a most preferred embodiment, the at least one base is selected from the group consisting of potassium carbonate, 4-dimethylaminopyridine and triethylamine. Step (B) of the present invention for the preparation of a compound of the general formula (III) is as follows and involves the steps from a) to f) a) reacting a nitro-methylphenyl compound of formula IV,

(IV),

wherein R² is Cl or C₁-C₄ alkyl, with an organic nitrile of the formula R5 -ONO, wherein R5 is n-butyl, in the presence of at least one base to give and oxime of the formula (V),

wherein R² is Cl or C₁-C₄ alkyl, b) cyclization of the oxime of the formula (V) with an alkene of the formula (VI), (VI), wherein R6, R7, R8 are, identical or different, hydrogen or C₁-C₄ alkyl, in the presence of at least one base to give a compound of formula (VII),

(VII),

wherein R² is Cl or C₁-C₄ alkyl and R3 is hydrogen or C₁-C₄ alkyl, c) reducing the compound of formula (VII) in the presence of at least one catalyst to give the compound of formula (VIII),

(VIII),

wherein R² is Cl or C₁-C₄ alkyl, and R3 is hydrogen or C₁-C₄ alkyl, d) substituting the para amino position in the compound of formula (VIII) to give the compound of formula (IX),

wherein R² is Cl or C₁-C₄ alkyl, R³ is hydrogen or C₁-C₄ alkyl and X is Cl, Br, I, S(=0)₂-CH₃ or S(=O)₂-CF₃; e) reacting the compound of formula (IX) with a dialkyl disulfide of formula (X)

wherein R⁴ is C₁-C₄ alkyl,

in the presence of an organic nitrile of the formula R⁵-ONO, wherein R⁵ is n-butyl, and at least one catalyst to give the compound of formula (XI),

wherein R² is Cl or Ci-C₄ alkyl, R³ is hydrogen or C₁-C₄ alkyl, R⁴ is C₁-C₄ alkyl, and X is Cl, Br, I, S(=O)₂-CH₃ or S(=O)₂-CF₃ f) oxidizing the compound of formula (XI) with at least one oxidizing agent to obtain the compound of formula (I II),

wherein X is Cl, Br, I, S(=0)₂-CH₃ or S(=0)₂-CF₃, R² is Cl or Ci-C₄ alkyl, R³ is hydrogen or Cl- C4 alkyl, and R⁴ is Ci-C₄ alkyl,

In an embodiment, R¹ is C₁_C₂ alkyl, R² is C₁-C₄ alkyl, R³ is hydrogen or C₁-C₄ alkyl, R⁴ is C₁-C₄ alkyl.

In another embodiment, R¹ is methyl, R² is C₁-C₂ alkyl, R³ is hydrogen or C₁-C₄ alkyl, R⁴ is C₁- C₄ alkyl.

In another embodiment, R¹ is methyl, R² is methyl, R³ is hydrogen or C₁-C₄ alkyl, R⁴ is C₁-C₄ alkyl.

In another embodiment, R¹ is methyl, R² is methyl, R³ is hydrogen, R⁴ is C₁-C₄ alkyl.

In yet another embodiment, R¹ is methyl, R² is methyl, R³ is hydrogen, R⁴ is C₁-C₂ alkyl.

In another embodiment, R¹ is methyl, R² is methyl, R³ is methyl, R⁴ is methyl.

In a preferred embodiment, R¹ is methyl, R² is methyl, R³ is hydrogen, R⁴ is methyl.

In an embodiment, R⁶, R⁷, R⁸ are, identical or different, hydrogen or C₁ C₄ alkyl

In another embodiment, R⁶, R⁷, R⁸ are, identical or different, hydrogen or C₁-C₂ alkyl

In an embodiment, X is Cl, Br, I, S(=0)₂-CH₃ or S(=0)₂-CF₃.

In yet another embodiment, X is Cl, Br, l,-CF₃.

In a preferred embodiment, X is Cl, Br.

In a most preferred embodiment, X is Br.

In an embodiment, step (B) takes place in the presence of at least one base, at least one metal catalyst and at least one solvent.

In an embodiment, the at least one base used in step (B) is selected from the group of tertiary amines, for example triethylamine, cyclic amines, such as N-methylpiperidine or N,N'- dimethylpiperazine, pyridine, alkali metal carbonates, for example sodium carbonate or potassium carbonate, alkali metal bicarbonates, for example sodium bicarbonate or potassium bicarbonate, alkaline earth metal carbonates, for example calcium carbonate, and alkali metal hydroxides, for example sodium hydroxide or potassium hydroxide.

In an embodiment, the at least one metal catalyst in step (B) is Ni, Pt/C, Pd/C, copper powder, elemental copper in a different form, such as, for example, turnings, wire, granules, pellets, rods; copper(l) salts, for example copper(l) chloride, copper(l) bromide or copper(l) iodide, copper(ll) salts, or elemental iodine.

In an embodiment, the at least one solvent in step (B) is a haloalkane, such as 1,2- dichloroethane or methylene chloride; aromatic compounds, such as benzene, toluene, chlorobenzene, nitrobenzene or xylene; polar aprotic solvents, for example N,N- dialkylformamides, N,N-dialkylacetamides, N-methylpyrrolidone, dimethylpropyleneurea; tetramethylurea, acetonitrile, propionitrile; alcohols, such as methanol, ethanol, n-propanol or isopropanol; carboxylic acids, such as acetic acid or propionic acid; carboxylic esters, such as ethyl acetate. In the following, there is provided a list of embodiments to further illustrate the present disclosure without intending to limit the disclosure to the specific embodiments listed below. 1. A process for the preparation of a compound of the general formula (I) or its salts,

wherein

R₁ is C₁-C₄ alkyl, R² is Cl or C 3

1-C₄ alkyl, R is hydrogen or C₁-C₄ alkyl and R⁴ is C₁-C₄ alkyl, comprising at least the step of reacting a compound of formula (II),

wherein

wherein X is Cl, Br, I, S(=O)₂-CH₃ or S(=O)₂-CF₃, R² is Cl or C₁-C₄ alkyl, R³ is hydrogen or C₁-C₄ alkyl, and R4 is C₁-C₄ alkyl, in the presence of carbon monoxide, at least one alkali metal iodide, at least one base, at least one metal catalyst and at least one phosphine compound. 2. The process according to embodiment 1, wherein the compound of general formula (III) is obtained by one or more of the following steps: a) reacting a nitro-methylphenyl compound of formula IV,

wherein R² is Cl or C₁-C₄ alkyl, b) cyclization of the oxime of the formula (V) with an alkene of the formula (VI),

wherein R⁶, R⁷, R⁸ are, identical or different, hydrogen or C₁-C₄ alkyl, in the presence of at least one base to give a compound of formula (VII),

wherein R² is Cl or C₁-C₄ alkyl and R³ is hydrogen or C₁-C₄ alkyl, c) reducing the compound of formula (VII) in the presence of at least one catalyst to give the compound of formula (VI II),

wherein R² is Cl or C₁-C₄ alkyl, and R³ is hydrogen or C₁-C₄ alkyl, d) substituting the para amino position in the compound of formula (VI II) to give the compound of formula (IX),

wherein R² is Cl or C₁-C₄ alkyl, R³ is hydrogen or Ci-C₄ alkyl and X is Cl, Br, I, S(=0)₂-CH₃ or S(=0)₂-CF₃; e) reacting the compound of formula (IX) with a dialkyl disulfide of formula (X) wherein R4 is C₁-C₄ alkyl,

wherein R² is Cl or C 3

1-C₄ alkyl, R is hydrogen or C₁-C₄ alkyl, R4 is C₁-C₄ alkyl, and X is Cl, Br, I, S(=O)₂-CH₃ or S(=O)₂-CF₃ f) oxidizing the compound of formula (XI) with at least one oxidizing agent to obtain the compound of formula (III),

wherein X is Cl, Br, I, S(=O)₂-CH₃ or S(=O)₂-CF₃, R is Cl or C₁-C₄ alkyl, R is hydrogen or C1- C4 alkyl, and R4 is C₁-C₄ alkyl,

3. The process according to embodiments 1 or 2, wherein R1, R² and R4 are each methyl and R3 is hydrogen. 4. The process according to embodiment 1, wherein the alkali metal iodide is selected from the group consisting of sodium iodide, potassium iodide and lithium iodide. form of a free state of formula M or in a form of a metal complex of formula M(L)n, wherein

M is selected from the group consisting of nickel (Ni), cobalt (Co), iron (Fe), 5 ruthenium (Ru), rhodium (Rh), palladium (Pd), iridium (Ir), platinum (Pt), silver (Ag), copper (Cu), zinc (Zn), molybdenum (Mo) and tungsten (W);

L is, identical or different, selected from the group consisting of Cl, Br, I, P(C₅-C₁₄- aryl)_m, P(C₅-C₁₂-heteroaryl)_m, P(C₅-C₁₂-heteroaryl)_m(C₅-C₁₄-aryl)_3-m, CN, C₁-C₆-alkyl, C₁- C₆-alkyl-O-C₁-C₆-alkyl, -O-CO-C₁-C₆-alkyl, OH, nitro, -O-C₁-C₆-alkyl, C₁-C₄-haloalkoxy,10 C₃-C₈-cycloalkyl, C₃-C₈-halocycloalkyl, C₃-C₈-cycloalkenyl, C₅-C₁₄-aryl, C₅-C₁₄-aryl- (CH₂)_o-(Q)_p-(CH₂)_o-C₅-C₁₄-aryl and 1,1ʼ- bis(diphenyl phosphino)ferrocene ; whereby Q represents a bridging group selected from the group consisting of -CR9R10, -O-, -S-, - NR11R12, -SiR13R14 and -CO-, wherein R9 and R10, identical or different, are hydrogen, C₁- C₁ alkyl, C₅-C₁₄-aryl or C₅-C₁₂-heteroaryl; wherein R11, R12, R13 and R14 2 , identical or 15 different, are hydrogen or C₁-C₄ alkyl or R11 together with R12 forms C₅-C₁₂-membered heterocycloalkyl, C₅-C₁₄-membered heterocycloalkenyl or C₅-C₁₂-membered heteroaryl; and L is unsubstituted or further substituted by 1, 2, 3, 4 or 5 identical or different groups selected from the group consisting of Cl; F; Br; I; CN; -NO₂; -NR10R11, -P(phenyl)₂, -OH, unsubstituted or substituted C₁-C₁₂-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, unsubstituted or20 substituted C₅-C₁₄-aryl, unsubstituted or substituted C₅-C₁₂-heteroaryl, C₅-C₁₂- membered heterocycloalkyl, C₅-C₁₄-membered heterocycloalkenyl, -O-(CH₂)_r-O-, - C(=O)R15

, -C(=O)-O-R16

, -C=N-R17, -SO₃H, -O-C₁-C₆-alkyl and -O-Si-C₁-C₄-alkyl; or L is supported on silica gel, dendrimers, polystyrenes or mesoporous siliceous foam,

25 wherein

R15 is hydrogen or C₁-C₄-alkyl;

R16 is hydrogen or C₁-C₄-alkyl;

R17 is hydrogen, C₁-C₁₂-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₅-C₁₄-aryl, C₅-C₁₂-heteroaryl or C₃-C₁₂-cycloalkyl;

30 n is 0, 1, 2, 3, 4, 5 or 6;

m is 1,2 or 3;

o is 0,1 or 2

p is 0,1 or 2 and

r is 1,2,3,4 or 5,

35 or their acceptable salts thereof. 6. The process according to embodiment 5, wherein M is selected from the group consisting of nickel (Ni), iron (Fe), palladium (Pd) and copper (Cu). 40 7. The process according to embodiment 5, wherein L is, identical or different, selected from the group consisting of Cl, Br, I, P(C₅-C₁₄-aryl)_m, CN, unsubstituted or substituted C₁-C₁₂-alkyl, C₁-C₄-alkoxy, C₃-C₈-cycloalkenyl, -O-CO-C₁-C₆-alkyl, C₅-C₁₄-aryl, 1,1ʼ- bis(diphenyl phosphino)ferrocene and C₅-C₁₄-aryl-(CH₂)_o-(Q)_p-(CH₂)_o-C₅-C₁₄-aryl, whereby m, o, Q and p are as defined as in claim 7. 8. The process according to embodiment 5, wherein the metal complex of formula M(L)n is selected from the group consisting of Pd(OCOCH₃)₂, PdCl₂, PdCl₂ (CH₃CN)₂, Pd (1,1ʼ- bis(diphenyl phosphino)ferrocene)Cl₂, Pd₂(dibenzylideneacetone)₃ and

Pd(dibenzylideneacetone)₂. 9. The process according to embodiments 5 to 8, wherein the at least one metal catalyst is in a form of a free state of palladium such as Pd/C or in a form of a metal complex selected from the group consisting of Pd(OCOCH₃)₂ and PdCl₂. 10. The process according to embodiment 1, wherein the at least one phosphine compound is of the formula PX₁X₂X₃ or (PX₁X₂)₂(B)_q, whereby X₁, X₂ and X₃, identical or different, are F, Cl, Br, I, -NR18R19

, hydrogen, -O-C₁-C₆-alkyl, -O-CO-C₁-C₆-alkyl, C₁-C₁₂-alkyl, C₂- C₆-alkenyl, C₂-C₆-alkynyl, C₅-C₁₄-aryl, C₅-C₁₂-heteroaryl, C₃-C₁₂-cycloalkyl, C₃-C₁₂- cycloalkenyl, C₃-C₁₂-heterocycloalkyl, C₃-C₁₄-heterocycloalkenyl or -Si-(C₁-C₁₂-alkyl)₃, whereby B is CR²0R²1, -O-, -phenyl-O-phenyl-, -S-, -NR18R19, -SiR²2R²3 or -C(=O)-, wherein R²0 and R²1, identical or different, are hydrogen, C₁-C₁₂-alkyl, C₅-C₁₄-aryl or C₅- C 1

1₂-heteroaryl, wherein R18, R19, R²0 and R² , identical or different, are hydrogen or C₁- C₄-alkyl or R18 together with R19 forms C5-C12-membered heterocycloalkyl, C₅-C₁₄- membered heterocycloalkenyl or C₅-C₁₂-heteroaryl; whereby X₁, X₂ and X₃ , identical or different, are unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or different groups selected from the group consisting of Cl; F; Br; I; CN; -NO₂; -NR18R19, -P(phenyl)₂, -OH, unsubstituted or substituted C₁-C₁₂-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, unsubstituted or substituted C₅-C₁₄-aryl, unsubstituted or substituted C₅-C₁₂-heteroaryl, -O-(CH₂)_r-O-, - C(=O)R²4

, -C(=O)-O-R²5

, -C=N-R²6, -SO₃H, -O-C₁-C₆-alkyl and -O-Si-C₁-C₄-alkyl, C₅-C₁₂- membered heterocycloalkyl, C₅-C₁₄-membered heterocycloalkenyl and C₅-C₁₂- heteroaryl;

wherein q is 1, 2, 3, 4, 5 or 6;

r is 1, 2 ,3, 4 or 5;

R²4 is hydrogen or C₁-C₄-alkyl;

R²5 is hydrogen or C₁-C₄-alkyl; and

R²6 is hydrogen, C₁-C₁₂-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₅-C₁₄-aryl, C₅-C₁₂ heteroaryl or C₃-C₁₂-cycloalkyl;

or their acceptable salts thereof. 11. The process according to embodiment 10, wherein the at least one phosphine

compound is selected from the group consisting of allyldiphenylphosphine; 1,3- bis(diphenylphosphino)propane; 1,3-bis(dicyclohexylphosphino)propane, 1,4- bis(diphenylphosphino)butane, di-tert-butyl(phenyl)phosphine , tri-tert- butylphosphine ,di-tert-butyl(phenyl)phosphine tetrafluoroborate; (2-ammonioethyl) di-tert-butylphosphonium bis(tetrafluoroborate); (2-ammonioethyl)

diisopropylphosphonium bis(tetrafluoroborate); (3-ammoniopropyl) di-tert- butylphosphonium bis(tetrafluoroborate); (3-ammoniopropyl) diisopropylphosphonium bis(tetrafluoroborate); bis(3,5-bis(trifluoromethyl)phenyl)(2¢,6¢-bis(isopropoxy)-3,6- dimethoxybiphenyl-2-yl)phosphine; benzyldiphenylphosphine; (2-biphenyl)di-1- adamantylphosphine; 1-[2-[bis(tert-butyl)phosphino]phenyl]-3,5-diphenyl-1H- pyrazole; bis[2-(diadamantylphosphino)ethyl]amine; 2-[bis(3,5-di-tert-butyl-4- methoxyphenyl)phosphino]benzaldehyde; 2,6-bis(di-tert- butylphosphinomethyl)pyridine; bis(dicyclohexylphosphinophenyl)ether;

bis(diethylamino)phenylphosphine; bis(dimethylamino)chlorophosphine; 2-[bis(3,5- dimethylphenyl)phosphino]benzaldehyde; bis[4-(3,3,4,4,5,5,5-heptafluoro-2,2- bis(trifluoromethyl)pentyl)phenyl]phenylphosphine; bis(2-methoxyphenyl)phosphine; bis[4-(1H,1H,2H,2H-perfluorodecyl)phenyl]phenylphosphine; 1,1¢- bis(phenylphosphinidene)ferrocene; (2-bromophenyl)dicyclohexylphosphine; (2- bromophenyl)diphenylphosphine; tert-butyldicyclohexylphosphine; tert- butyldicyclohexylphosphonium tetrafluoroborate; tert-butyldiisopropylphosphine; tert- butyldiphenylphosphine; 1-(dicyclohexylphosphino)-2,2-Diphenyl-1- methylcyclopropane; cyclohexyldiphenylphosphine; di(1-adamantyl)-2- dimethylaminophenylphosphine; di-1-adamantylphosphine; di(1-adamantyl)-(2- triisopropylsiloxyphenyl)phosphine; (5H-dibenzo[a,d]cyclohepten-5- yl)diphenylphosphine; di-tert-butylcyclohexylphosphine; di-tert-butyl N,N- diisopropylphosphoramidite; di-tert-butylmethylphosphine; di-tert- butyl(methyl)phosphonium tetrafluoroborate; di-tert-butyl(methyl)phosphonium tetrafluoroborate; di-tert-butylneopentylphosphine; di-tert- butylneopentylphosphonium tetrafluoroborate; di-tert-butylphenylphosphine; di-tert- butylphosphate potassium salt; 2¢-(di-tert-butylphosphino)acetophenone ethylene ketal; 2-(di-tert-butylphosphino)dimethylaminobenzene; 2-(di-tert- butylphosphino)ethylamine; 2-((di-tert-butylphosphinomethyl)-6- diethylaminomethyl)pyridine; 5-(di-tert-butylphosphino)-1-(naphthalen-1-yl)-1H- pyrazole; 5-(di-tert-butylphosphino)-1¢, 3¢, 5¢-triphenyl-1¢H-[1,4¢]bipyrazole; 3- (di-tert-butylphosphonium)propane sulfonate; P,P-dichloroferrocenylphosphine;

dicyclohexyl-(2,6-diisopropylphenyl)phosphine; dicyclohexyl(4-(N,N- dimethylamino)phenyl)phosphine; dicyclohexyl(ethyl)phosphine; dicyclohexyl(4- isopropylphenyl)phosphine; dicyclohexyl(2-methylphenyl)phosphine;

dicyclohexylphenylphosphine; 2¢-(dicyclohexylphosphino)acetophenone ethylene ketal; 2-(dicyclohexylphosphino)benzophenone; 2-(dicyclohexylphosphino)-N,N- diisopropyl-1H-indole-1-carboxamide; N -(dicyclohexyl phosphino)-2-(2¢- methoxyphenyl)indole; 2-[(dicyclohexylphosphino)methyl]-1,3-bis(2,6- diisopropylphenyl)-4,5-dimethylimidazolium iodide; 2-(2- dicyclohexylphosphinophenyl)-1,3-dioxolane; 2-[2-(dicyclohexylphosphino)phenyl]-N- methylindole; dicyclohexyl(2,4,6-trimethylphenyl)phosphine; diethylphenylphosphine; diethylphosphine; 4-(diethylphosphino)-N,N-dimethylaniline; 9-[2- (diisopropylphosphino)phenyl]-9H-carbazole; 2-[di(2- methoxyphenyl)phosphino]benzenesulfonic acid;

dimethylaminophenylchlorophosphine; 4-(dimethylamino)phenyldiphenylphosphine; 2- (1,1-dimethylpropyl)-6-(diphenylphosphino)pyridine; diphenyl(2- methoxyphenyl)phosphine; 4-diphenylphosphanylbenzoic acid; 2- (diphenylphosphino)benzaldehyde; 2-(diphenylphosphino)benzaldehyde oxime; 3- (diphenylphosphino)benzenesulfonic acid sodium salt; 2-(diphenylphosphino)benzoic acid; 4-(diphenylphosphino)benzoic acid; N-[2-(diphenylphosphino)benzylidene] cyclohexylamine; 2-(diphenylphosphino)-N,N-dimethylbenzylamine; 2- (diphenylphosphino)ethanaminium tetrafluoroborate; 2- (diphenylphosphino)ethylamine; 2-(2-(diphenylphosphino)ethyl)pyridine; 3- (diphenylphosphino)propan-1-aminium tetrafluoroborate; 3-(diphenylphosphino)-1- propylamine; 4-(diphenylphosphino) styrene; 2-(diphenylphosphino)-N,N,N- trimethylbenzylammonium triflate;diphenyl-2-pyridylphosphine; diphenyl(o- tolyl)phosphine; diphenyl(p-tolyl)phosphine; diphenylvinylphosphine; 2-(di-p- tolylphosphino)benzaldehyde; ethyldiphenylphosphine; [4- (3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl)phenyl] diphenylphosphine; (4-hydroxyphenyl)diphenylphosphine; isopropyldiphenylphosphine; 1-methyl-2-(2- dicyclohexylphosphinophenyl)-1H-benzoimidazole; 1-methyl-2-(2- diisopropylphosphinophenyl)-1H-benzoimidazole; methyldiphenylphosphine; 1- methyl-2-(2-diphenylphosphinophenyl)-1H-benzoimidazole; 1,2,3,4,5-pentaphenyl- 1¢-(di-tert-butylphosphino)ferrocene; phenylbis[4-(3,3,4,4,5,5,6,6,7,7,8,8,8- tridecafluorooctyl)phenyl]phosphine; phenyldi(o-tolyl)phosphine; phenylphosphine; 4,4¢-(phenylphosphinidene)bis(benzenesulfonic acid) dipotassium salt hydrate; tetrapropylphosphonium bromide; triallylphosphine; tribenzylphosphine;

tributylphosphine; tri-n-butylphosphine; tri-tert-butylphosphine; tri-tert- butylphosphine; tri-tert-butylphosphine; tributylphosphine tetrafluoroborate; tri-tert- butylphosphonium tetrafluoroborate; tricyclohexylphosphine; tricyclohexylphosphine; tricyclohexylphosphine; tricyclohexylphosphine tetrafluoroborate;

tricyclopentylphosphine; tricyclopentylphosphine tetrafluoroborate; triethylphosphine; triethylphosphine; ((4-trifluoromethyl)phenyl)di-tert-butylphosphine, tri(2- furyl)phosphine; ((2,4,6-tri-isopropyl)phenyl)di-cyclohexylphosphine;

triisopropylphosphine; triisopropylphosphonium tetrafluoroborate; trimethylphosphine; trimethylphosphonium tetrafluoroborate; tri-1-naphthylphosphine; trioctylphosphine; triphenylphosphine; triphenylphosphine hydrobromide; 4- (triphenylphosphonio)butane-1-sulfonate; tripropylphosphine; tris[3,5- bis(trifluoromethyl)phenyl]phosphine; tris(4-chlorophenyl)phosphine;

tris(diethylamino)phosphine; tris(2,6-dimethoxyphenyl)phosphine;

tris(dimethylamino)phosphine; tris(3,5-dimethylphenyl)phosphine; tris(2,4-dimethyl-5- sulfanatophenyl)phosphine trisodium salt; tris[2-(diphenylphosphino)ethyl]phosphine; tris(4-fluorophenyl)phosphine; tris[4-(heptadecafluorooctyl)phenyl]phosphine;

tris(hydroxymethyl)phosphine; tris(4-methoxy-3,5-dimethylphenyl)phosphine; tris(o- methoxyphenyl)phosphine; tris(4-methoxyphenyl)phosphine; tris(4-methyl-1- piperazinyl)phosphine; tris(pentafluorophenyl)phosphine; tris(1- pyrrolidinyl)phosphine; tris[4-(tridecafluorohexyl)phenyl]phosphine; tris[4- (3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)phenyl]phosphine; tris(4- trifluoromethylphenyl)phosphine; tris(2,4,6-trimethoxyphenyl)phosphine; tris(2,4,6- trimethylphenyl)phosphine; tris(trimethylsilyl)phosphine; tri(o-tolyl)phosphine; tri(p- tolyl)phosphine; tri-o-tolylphosphine tetrafluoroborate; and 2- (dicyclohexylphosphino)-3,6-dimethoxy-2¢,4¢,6¢-triisopropyl-1,1¢-biphenyl or acceptable salts thereof.

12. The process according to claim 11, wherein the at least one phosphine compound is selected from the group consisting of triphenylphosphine, 1,3- bis(dicyclohexylphosphino)propane, 1,4-bis(diphenylphosphino)butane, di-tert- butyl(phenyl)phosphine and tri-tert-butylphosphine. 13. The process according to embodiment 1, wherein the at least one base is selected from the group consisting of organic bases and inorganic bases. 14. The process according to embodiment 13, wherein the organic bases are selected from the group consisting of N(R²7)₃, N-methyl piperidine, N-methyl pyrrolidine, N-methyl morpholine, piperidine, dimethyl amino pyridine, pyridine, lithium hexamethyldisilazide, sodium hexamethyldisilazide and tetra-C₁-C₆-alkyl ammonium hydroxide, wherein R²7 is, identical or different, hydrogen, C₁-C₆-alkyl, C₅-C₁₄-aryl, or C₃-C₆-cycloalkyl. 15. The process according to embodiment 13, wherein the inorganic bases are selected from the group consisting of alkali metal hydroxide, alkaline earth hydroxide, alkali metal bicarbonate, alkaline earth bicarbonate, alkali metal carbonate, alkaline earth carbonate, alkali metal phosphate, alkali metal alkoxide and alkaline earth alkoxide. 16. The process according to embodiment 15, wherein the alkali metal hydroxide is

selected from group consisting of lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide and cesium hydroxide;

wherein the alkaline earth hydroxide is selected from the group consisting of magnesium hydroxide, calcium hydroxide, strontium hydroxide and barium hydroxide; wherein the alkali metal bicarbonate is selected from the group consisting of lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, rubidium bicarbonate and cesium bicarbonate;

wherein the alkaline earth bicarbonate is selected from the group consisting of magnesium bicarbonate, calcium bicarbonate, strontium bicarbonate and barium bicarbonate;

wherein the alkali metal carbonate is selected from the group consisting of lithium carbonate, sodium carbonate, potassium carbonate, rubidium carbonate and cesium carbonate;

wherein the alkaline earth carbonate is selected from group the consisting of magnesium carbonate, calcium carbonate, strontium carbonate and barium carbonate; wherein the alkali metal phosphate is selected from the group consisting of

monosodium phosphate, disodium phosphate, trisodium phosphate, monopotassium phosphate, dipotassium phosphate and tripotassium phosphate;

wherein the alkali metal alkoxide is selected from the group consisting of NaOR²8, KOR²8, RbOR²8 and CsOR²8; wherein the alkaline earth alkoxide is selected from the group consisting of Mg(OR²8)₂, Ca(OR²8)₂ and Ba(OR²8)₂; wherein R²8 is, identical or different, C₁-C₄-alkyl. 17. The process according to embodiment 16, wherein the at least one inorganic base is selected from the group consisting of sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, monosodium phosphate, disodium phosphate, trisodium phosphate, monopotassium phosphate, dipotassium phosphate and tripotassium phosphate. 18. The process according to embodiments 13 to 17, wherein the at least one base is selected from the group consisting of potassium carbonate, 4-dimethylaminopyridine and triethylamine. 19. The process according to embodiment 1, wherein the process is performed in the presence of at least one solvent which is selected from the group consisting of esters, ethers, aromatic hydrocarbons and acetals. 20. The process according to embodiment 19, wherein the esters are selected from the group consisting of triethylorthoformate, trimethylorthoformate, tripropylorthoformate and tributylorthoformate. 21. The process according to embodiment 19, wherein the ethers are selected from the group consisting of tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, diethyl ether, diisopropyl ether, di-n-propyl ether, di-n-butyl ether, methyl-tert-butyl ether, diisobutyl ether and tetrahydropyran. 22. The process according to embodiment 19, wherein the acetals are selected from the group consisting of dimethoxymethane, dimethoxypropane and dimethoxybutane. 23. The process according to embodiment 19, wherein the aromatic hydrocarbons are selected from the group consisting of toluene, xylene, cyclohexane and monochlorobenzene. 24. The process according to embodiment 1, wherein the ratio of the at least one metal catalyst to the at least one compound of formula (III) is in the range of 1:100 moles to 1:500 moles. 25. The process according to embodiment 1, wherein the mole ratio of the at least phosphine compound to the at least one metal catalyst is in the range of 1:0.075 to1:0.015. 26. The process according to embodiment 1, wherein the process is performed at a temperature in the range of 50 °C to 150 °C. 27. The process according to embodiment 1, wherein the process is performed at a pressure in the range of 5 bar to 20 bar. 28. The process according to embodiment 1, wherein the compound of the general formula (I) or its salts are isolated by at least one of the following steps: a) filtering the reaction mixture through celite bed to remove the catalyst and washing the bed with water,

b) concentrating the filtrate to remove the solvent and water,

c) diluting the concentrated mass with alcohol,

d) heating the reaction mixture of step c) to 60ºC and adjusting the pH to1.5 using 35% hydrochloric acid,

e) cooling the reaction mixture to 20ºC and separating the product by filtration, f) drying the product at 70 ºC -75 ºC under vacuum for 12 hours to isolate the compound of formula (I). EXAMPLES The characterization can be done by High Performance Liquid chromatography General Procedure: With due modification of the starting compounds, the compound of formula (I) can be prepared by procedures as given in below schemes. Example 1: Preparation of [3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]- (5-hydroxy-1-methyl-pyrazol-4-yl)methanone. A round bottom flask (RBF) was charged with 22 gm (0.069 moles) of 3-(3-bromo-2-methyl- 6-methylsulfonyl-phenyl)-4,5-dihydroisoxazole followed by 100 gm of 1,4-dioxane and stirred it for 15 min. 17.6 gm (0.127 moles) of potassium carbonate was then charged in the round bottom flask. The reaction mixture was refluxed, and 50 gm of solvent was distilled off atmospherically. The slurry formed was then cooled to 25°C and transferred to clean pressure reactor, followed by addition of 6.8 gm (0.069 moles) of 2-methylpyrazol-3-ol, 2.07 gm (0.013 moles) of Sodium iodide, 0.72 gm (0.0027 moles) of Triphenylphosphine and 130 gm 1,4-dioxane. This reaction mixture was flushed with carbon monoxide gas, heated and stirred at 60°C for 30 min under carbon monoxide atmosphere. The reaction mixture was later cooled to 30°C. 0.88 gm (0.0003 moles) of Pd/C (RD-383) was added to the reaction mixture and the reaction mass was flushed with carbon monoxide gas and the reaction mixture was heated to 120°C under pressure of 15 bar of carbon monoxide gas for 20 hours. The reaction mass is then cooled to 60°C and the reactor was depressurized. 200 gm of water was added to the reaction mixture and was filtered through celite bed to remove catalyst and further the bed was washed with water. The filtrate was concentrated to remove 1,4-dioxane and water and the concentrated reaction mass was then diluted with 125 gm methanol. This reaction mixture was heated to 60°C and pH of reaction mixture was adjusted to 1.5 using 35% hydrochloric acid. The reaction mixture was then cooled to 20°C within 3- 4 hours and the product was separated by filtration. The filtered product was then dried at 70-75°C under vacuum for 12 hours. The isolated product (i.e. [3-(4,5-dihydroisoxazol-3-yl)- 2-methyl-4-methylsulfonyl-phenyl]-(5-hydroxy-1-methyl-pyrazol-4-yl)methanone) had a yield of 84.4% with purity of 99.37%. Example 2: Preparation of [3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]- (5-hydroxy-1-methyl-pyrazol-4-yl)methanone A pressure reactor was charged with 22 gm (0.069 moles) of 3-(3-bromo-2-methyl-6- methylsulfonyl-phenyl)-4,5-dihydroisoxazole followed by 180 gm 1,4-dioxane, 17.6 gm (0.12 moles) of Potassium Carbonate, 0.72 gm (0.0027 moles) of triphenylphosphine and 6.8 gm (0.069 moles) of 2-methylpyrazol-3-ol. This reaction mixture was flushed with carbon monoxide gas then heated and stirred at 60°C for 30 min under carbon monoxide atmosphere. The reaction mixture was cooled to 30°C and 0.071 gm (0.0004 moles) Palladium Chloride catalyst was added to the reaction mixture and the reaction mass was flushed with carbon monoxide gas. The reaction mixture was heated to 120°C under pressure of 15 bar of carbon monoxide gas for 20 hours. The reaction mass was then cooled to 60°C followed by depressurizing the reactor. Further 200 gm of DM water was added to reaction mixture followed by 0.7 gm activated carbon and the reaction mixture was filtered through the celite bed to remove catalyst and the bed was washed with 100 gm water. The main filtrate and the washings were combined and were concentrated to remove 1,4-dioxane and water. The concentrated reaction mass was then diluted with 125 gm methanol and further the reaction mixture was heated to 60°C and the pH of reaction mixture was adjusted to 1.5 using 35% hydrochloric acid. The reaction mixture was then cooled to 20°C over a period of 3-4 hours and the product was separated by filtration. The filtered product was then dried at 70-75°C under vacuum for 12 hours. The isolated product ( i.e. [3-(4,5- dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-(5-hydroxy-1-methyl-pyrazol-4- yl)methanone) had a yield of 76% with a purity of 99.81%. Example 3 to 10 were performed as per examples 1, however the reaction conditions for the same are illustrated in table 2. The above examples do not restrict the invention in any manner.

.6 .8 .0 .0 .6 .4 .0 .9

Purity of the isolated product: at least 99%

Claims

Claims:

1. A process for the preparation of a compound of the general formula (I) or its salts,

wherein

R¹ is C₁-C₄ alkyl, R² is Cl or C₁-C₄ alkyl, R³ is hydrogen or C₁-C₄ alkyl and R⁴ is C₁-C₄ alkyl, comprising at least the step of reacting a compound of formula (II),

wherein

wherein

X is Cl, Br, I, S(=0)₂-CH₃ or S(=0)₂-CF₃, R² is Cl or C₁-C₄ alkyl, R³ is hydrogen or C₁-C₄ alkyl, and R⁴ is C₁-C₄ alkyl, in the presence of carbon monoxide, at least one alkali metal iodide, at least one base, at least one metal catalyst and at least one phosphine compound.

2. The process according to claim1, wherein the compound of general formula (III) is obtained by one or more of the following steps: a) reacting a nitro-methylphenyl compound of formula IV,

(IV),

(VII),

(VIII),

wherein R² is Cl or C₁-C₄ alkyl, R3 is hydrogen or C₁-C₄ alkyl and X is Cl, Br, I, S(=O)₂-CH₃ or S(=O)₂-CF₃; e) reacting the compound of formula (IX) with a dialkyl disulfide of formula (X) (X) wherein R4 is C₁-C₄ alkyl,

wherein R² is Cl or C 3

(III),

wherein X is Cl, Br, I, S(=O)₂-CH₃ or S(=O)₂-CF₃, R² is Cl or C₁-C₄ alkyl, R³ is hydrogen or C1- C4 alkyl, and R4 is C₁-C₄ alkyl,

3. The process according to claim 1 or 2, wherein R¹, R² and R4 are each methyl and R³ is hydrogen. 4. The process according to claim 1, wherein the alkali metal iodide is selected from the group consisting of sodium iodide, potassium iodide and lithium iodide. 5. The process according to claim 1, wherein the at least one metal catalyst is in a form of a free state of formula M or in a form of a metal complex of formula M(L)n,

wherein M is selected from the group consisting of nickel (Ni), cobalt (Co), iron (Fe), ruthenium (Ru), rhodium (Rh), palladium (Pd), iridium (Ir), platinum (Pt), silver (Ag), copper (Cu), zinc (Zn), molybdenum (Mo) and tungsten (W);

L is, identical or different, selected from the group consisting of Cl, Br, I, P(C₅-C₁₄- aryl)_m, P(C₅-C₁₂-heteroaryl)_m, P(C₅-C₁₂-heteroaryl)_m(C₅-C₁₄-aryl)_3-m, CN, C₁-C₆-alkyl, C₁- C₆-a I ky I -0-Ci-C₆-a I ky I , -0-CO-C₁-C₆-alkyl, OH, nitro, -0-Ci-C₆-a I kyl , C₁-C₄ haloalkoxy, C₃-C₈-cycloalkyl, C₃-C₈-halocycloalkyl, C₃-C₈-cycloalkenyl, C₅-C₁₄-aryl, C₅-C₁₄-aryl- (CH₂)_o-(Q)_p-(CH₂)_o-C5-C₁₄-aryl and 1,1’- bis(diphenyl phosphino)ferrocene ; whereby Q represents a bridging group selected from the group consisting of -CR⁹R¹⁰, -0-, -S-, - NR¹¹R¹², -Si R¹³R¹⁴ and -CO-, wherein R⁹ and R¹⁰, identical or different, are hydrogen, C₁-C₁₂ alkyl, C₅-C₁₄-aryl or C₅-C₁₂-heteroaryl; wherein R¹¹, R¹², R¹³ and R¹⁴, identical or different, are hydrogen or C₁-C₄ alkyl or R¹¹ together with R¹²forms C₅-C₁₂-membered heterocycloalkyl, C₅-C₁₄-membered heterocycloalkenyl or C₅-C₁₂-membered heteroaryl; and L is unsubstituted or further substituted by 1, 2, 3, 4 or 5 identical or different groups selected from the group consisting of Cl; F; Br; I; CN; -N0₂; -NR¹⁰ R¹¹, - P(phenyl)₂, -OH, unsubstituted or substituted C₁-C₁₂-a I ky I , C₂-C₆-alkenyl, C₂-C₆- alkynyl, unsubstituted or substituted C₅-C₁₄-aryl, unsubstituted or substituted C₅-C₁₂- heteroaryl, C₅-C₁₂-membered heterocycloalkyl, C₅-C₁₄-membered heterocycloalkenyl, - 0-(CH₂)_r-0-, -C(=0)R¹⁵.-C(=0)-0-R¹⁶ _, -C=N-R¹⁷, -S0₃H, -O-C₁-C₆-alkyl and -O-Si-C₁- C₄-a I ky I ; or

L is supported on silica gel, dendrimers, polystyrenes or mesoporous siliceous foam,

wherein

R¹⁵ is hydrogen or C₄-C₄-a I ky I ;

R¹⁶ is hydrogen or C₄-C₄-a I ky I ;

R¹⁷ is hydrogen, C₁-C₁₂-a I ky I , C₂-C₆-alkenyl, C₂-C₆-a I ky ny I , C₅-C₁₄-aryl, C₅-C₁₂-heteroaryl or C₃-C₁₂-cycloalkyl;

n is 0, 1, 2, 3,

4,

5 or 6;

m is 1,2 or 3;

o is 0,1 or 2

p is 0,1 or 2 and

r is 1,2, 3, 4 or 5,

or their acceptable salts thereof.

6. The process according to claim 5, wherein M is selected from the group consisting of nickel (Ni), iron (Fe), palladium (Pd) and copper (Cu).

7. The process according to claim 5, wherein Lis, identical or different, selected from the group consisting of Cl, Br, I, P(C₅-C₁₄-aryl)_m, CN, unsubstituted or substituted C₁-C₁₂- alkyl, C₁-C₄ alkoxy, C₃-C₈-cycloalkenyl, -0-CO-C_!-C₆-alkyl, C₅-C₁₄-aryl, 1,1’- bis(diphenyl phosphino)ferrocene and C₅-C₁₄-aryl-(CH₂)₀-(Q)_p-(CH₂)₀-C₅-C₁₄-aryl, whereby m, o, Q and p are as defined as in claim 7.

8. The process according to claim 1, wherein the at least one phosphine compound is of the formula RC₄C₂C₃ or (RC₁C₂)₂(B)_F whereby X₄, X₂and X₃, identical or different, are F, Cl, Br, I, -NR¹⁸R¹⁹. hydrogen, -O-C₁-C₆-alkyl, -O-CO-C₁-C₆-alkyl, C₁-C₁₂-alkyl, C₂-C₆- alkenyl, C₂-C₆-a I ky ny I , C₅-C₁₄-aryl, C₅-C₁₂-heteroaryl, C₃-C₁₂-cycloalkyl, C₃-C₁₂- cycloalkenyl, C₃-C₁₂-heterocycloalkyl, C₃-C₁₄-heterocycloalkenyl or -Si- (C₁-C₁₂-a I ky l)₃, whereby B is CR²⁰R²¹, -0-, -phenyl-O-phenyl-, -S-, -NR¹⁸R¹⁹, -Si R²²R²³ or -C(=0)-, wherein R²⁰ and R²¹, identical or different, are hydrogen, C₁-C₁₂-a I ky I , C₅-C₁₄-aryl or C₅- C₁₂-heteroaryl, wherein R¹⁸, R¹⁹, R²⁰ and R²¹, identical or different, are hydrogen or C₄- C₄-a I ky I or R¹⁸ together with R¹⁹9forms C5-C12-membered heterocycloalkyl, C₅-C₁₄- membered heterocycloalkenyl or C₅-C₁₂-heteroaryl; whereby X₄, X₂and X₃ , identical or different, are unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or different groups selected from the group consisting of Cl; F; Br; I; CN; -N0₂; -NR¹⁸R¹⁹, - P(phenyl)₂, -OH, unsubstituted or substituted C₁-C₁₂-a I ky I , C₂-C₆-alkenyl, C₂-C₆- a I ky ny I , unsubstituted or substituted C₅-C₁₄-aryl, unsubstituted or substituted C₅-C₁₂- heteroaryl, -0-(CH₂)_r-0-, -C(=0)R²⁴ -C(=0)-0-R²⁵. -C=N-R²⁶, -S0₃H, -O-C₁-C₆-alkyl and -0-Si-C₁-C₄-a I ky I , C₅-C₁₂-membered heterocycloalkyl, C₅-C₁₄-membered

heterocycloalkenyl and C₅-C₁₂-heteroaryl;

wherein q is 1, 2, 3, 4, 5 or 6;

r is 1, 2 ,3, 4 or 5;

R²⁴ is hydrogen or C₄-C₄-a I ky I ;

R²⁵ is hydrogen or C₄-C₄-a I ky I ; and

R²⁶ is hydrogen, C₁-C₁₂-a I ky I , C₂-C₆-alkenyl, C₂-C₆-a I ky ny I , C₅-C₁₄-aryl, C₅-C₁₂ heteroaryl or C₃-C₁₂-cycloalkyl;

or their acceptable salts thereof.

9. The process according to claim 1, wherein the at least one base is selected from the group consisting of organic bases and inorganic bases.

10. The process according to claim 9, wherein the organic bases are selected from the group consisting of N(R²⁷)₃, N-methyl piperidine, N-methyl pyrrolidine, N-methyl morpholine, piperidine, dimethyl amino pyridine, pyridine, lithium hexamethyldisilazide, sodium hexamethyldisilazide and tetra-Ci-C₆-alkyl ammonium hydroxide, wherein R²⁷ is, identical or different, hydrogen, Ci-C₆-alkyl, C₅-C₁₄-aryl, or C₃-C₆-cycloalkyl.

11. The process according to claim 9, wherein the inorganic bases are selected from the group consisting of alkali metal hydroxide, alkaline earth hydroxide, alkali metal bicarbonate, alkaline earth bicarbonate, alkali metal carbonate, alkaline earth carbonate, alkali metal phosphate, alkali metal alkoxide and alkaline earth alkoxide.

12. The process according to claim 1, wherein the process is performed in the presence of at least one solvent which is selected from the group consisting of esters, ethers, aromatic hydrocarbons and acetals.

13. The process according to claim 1, wherein the ratio of the at least one metal catalyst to the at least one compound of formula (II I) is in the range of 1:100 to 1:500 moles.

14. The process according to claim 1, wherein the ratio of the at least phosphine compound to the at least one metal catalyst is in the range of 1:0.010 to 1:0.2.

15. The process according to claim 1, wherein the process is performed at a temperature in the range of 50 ° C to 150 ° C.

16. The process according to claim 1, wherein the process is performed at a pressure in the range of 5 bar to 20 bar.

17. The process according to claim 1, wherein the compound of the general formula (I) or its salts are isolated by at least one of the following steps: a) filtering the reaction mixture through celite bed to remove the catalyst and

washing the bed with water,

b) concentrating the filtrate to remove the solvent and water,

c) diluting the concentrated mass with alcohol,

d) heating the reaction mixture of step c) to 60°C and adjusting the pH tol.5 using

35% hydrochloric acid,

e) cooling the reaction mixture to 20°C and separating the product by filtration, f) drying the product at 70 °C -75 °C under vacuum for 12 hours to isolate the compound of formula (I).