(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
`
`(19) World Intellectual Property Organi7-ation
`International Bureau
`
`(43) International Publication Date
`1 November 2007 (01.11.2007)
`
`PCT
`
`(51) International Patent Classification:
`COlD 231144 (2006.01)
`
`(21) International Application Nnmber:
`PCT/fB2006/000999
`
`(22) International Filing Date:
`
`25 April 2006 (25.04.2006)
`
`(25) Filing Language:
`
`(26) Publication Language:
`
`English
`
`English
`
`(71) Applicant (jar all designated States except US):
`GHARDA CHEMICALS LIMITED
`[IN/fN];
`Jer
`Mansion, W.P. Warde Road (off Turner Road), Bandra,
`Mumbai, India 400050 (IN).
`
`(72) Inventors; and
`(75) Inventors/Applicants (jar US only): GHARDA, Keki,
`Horrnusji [IN/fN]; Gharda Chemicals Limited, B-27/29
`MIDC, Phase 1, Dombivli 421203, Maharashtra, India
`(IN) . .MALTE, Ashokkurnar, Maganlal [IN/INl; Gharda
`Chemicals Limited, B-27/29 MIDC, Phase 1, Dombivli
`421203, Maharashtra, India (IN) . .JOSEPH, Pulinattu,
`Cherian [IN/IN]; Gharda Chemicals Limited, B-27/29
`MIDC, Phase I, Dom bivli 421203, Maharashtra, India
`(IN). PARKAR, Sureshkurnar, Dattatraya [IN/IN];
`Gharda Chemicals Limited, B-27/29 MIDC, Pha~e 1,
`Dombivli 421203, Maharashtra, India (IN). SATHE,
`
`11111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111
`
`(10) International Publication Number
`WO 2007/122440 Al
`Shekhar, Vishwanath
`[IN/fN]; Gharda Chemicals
`Limited, B-27/29 MIDC, Phase 1, Dombivli 421203, Ma(cid:173)
`harashtra, India (IN). DAMANIA, Pragnesh, Dalpatrarn
`[IN/IN]; Gharda Chemicals Limited, B-27/29 MIDC,
`Phase 1, Dombivli 421203, Maharashtra, India (IN).
`(81) Designated States (unless otlletwise indicated, for every
`kind of national protection available): AE, AG, AL, AM,
`A'C AU, AZ, BA, BB, BG, BR, BW, BY, BZ, CA, CH, CN,
`CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, FI,
`GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE,
`KG, KM, KN, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV,
`LY, MA, MD, MG, MK, MN, MW, MX, MZ, NA, NG, NI,
`NO, NZ, OM, PG, PH, PL, PT, RO, RU, SC, SD, SE, SG,
`SK, SL, SM, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US,
`UZ, VC, VN, YU, ZA, ZM, ZW.
`(84) Designated States (unless otlletwise indicated, for every
`kind of regional protection available): ARIPO (BW, GH,
`GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM,
`ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM),
`European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI,
`FR, GB, GR, HU, IE, IS, IT, LT, LU, LV, MC, NL, PL, PT,
`RO, SE, SI, SK, TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA,
`GN, GQ, GW, ML, MR, NE, SN, TD, TG).
`
`Published:
`with international search repon
`
`[Continued on next page]
`
`(54) Title: PROCESS FOR THE PREPARATION OF FIPRONIL, AN INSECTICIDE, AND RELATED PYRAZOLES
`
`(I)
`
`(57) Abstract: This
`the preparation of
`to a process for
`invention relates
`5-amino-1-phenyl-3-cyano-4-trifluoromethyl sulphinyl pyrazoles as defined by
`Formula- I, wherein: Rl = trif luoromethyl or trif luoromcthoxy, and R2, R3
`= individually hydrogen, chlorine or bromine , the process comprising the step
`of oxidizing a compound of Formula- 11, wherein: R1 = trifluoromethyl or trif
`luoromethoxy, and R2, R3 =individually hydrogen, chlorine or bromine, in a medium
`comprising at least one oxidizing agent and trichloro acetic acid, and/or the reactions
`product (s) of the at least one oxidizing agent and trichloro acetic acid, and at least
`one melting point depressant. The preferred pyrazole is Fipronil, preferably prepared
`using hydrogen peroxide and dichloro acetic acid at room temperature .
`
`(II)
`
`FINCHIMICA EXHIBIT 2013
`ADAMA MAKHTESHIM v. FINCH/MICA
`CASE IPR2016-00577
`
`---
`---
`
`----
`
`

`
`W 0 2007/122440 A 1
`
`lllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllll
`
`For two-letter codes and other abbreviations, refer to the "Guid(cid:173)
`ance Notes on Codes and Abbreviations" appearing at the begin(cid:173)
`ning of each regular issue of the PCT Gazette.
`
`

`
`WO 2007/122440
`
`PCT/IB2006/000999
`
`PROCESS FOR THE PREPARATION OF FIPRONIL, AN
`
`INSECTICIDE, AND RELATED PYRAZOLES
`
`BACKGROUND OF THE INVENTION
`
`5
`
`This
`
`invention relates to the preparation of 5-amino-1-
`
`pheny~-3-cyano-4-trifluoromethyl
`
`sulphinyl
`
`pyrazole
`
`pesticides as defined by formula-I below/ and in particular
`
`to
`
`5-amino-1-(2 1 6-dichloro-4-trifluoromethylphenyl)-3-
`
`10
`
`cyano-4-trifluoromethyl
`
`sulphinyl
`
`pyrazole.
`
`This
`
`pesticide 1 known as Fipronilr titled in Pesticide Manualr
`
`13th edition 1 entry No. 354 1 is an important insecticide and
`
`was invented by Rhone Poulenc (now BASF AG) in 1987.
`
`15
`
`The known commercial process for the manufacture of this
`
`compound uses corrosive and expensive chemicals such as
`
`trifluoro acetic acid. This process needs considerable
`
`improvement to make it economically viable. Research for
`
`an alternative has led to the invention disclosed herein.
`
`20
`
`SUMMARY OF THE INVENTION
`
`The main object of the present invention is successfully to
`
`substitute the corrosive and expensive solvent trifluoro
`
`25
`
`acetic acid with an inexpensive and easily available but
`
`effective alternative sol vent. Although
`
`the structurally
`
`1
`
`CONFIRMATION COPY
`
`

`
`wo 2007/122440
`
`PCT /IB2006/000999
`
`related
`
`compound
`
`trichloro acetic acid was
`
`initially
`
`considered.to be unsuitable because it is not a liquid at
`
`room temperature, it has been found that this compound can
`
`be made
`
`to be an effective solvent
`
`in
`
`the proposed
`
`5 manufacturing process
`
`through
`
`the use of a compatible
`
`melting ·point depressant which does not adversely affect
`
`the process,
`
`such as monochloro acetic acid, dichloro
`
`acetic acid, methylene dichloride, ethylene dichloride,
`
`monochlorobenzene or a haloalkane.
`
`10
`
`The present invention relates to an
`
`improved process of
`
`oxidation
`
`of
`
`5-amino-1-phenyl-3-cyano-4-trifluoromethyl
`
`sulphinyl pyrazoles using an oxidizing agent, preferably
`
`hydrogen peroxide, in a medium comprising trichloro acetic
`
`15
`
`acid as a substitute for the hitherto used expensive and
`
`corrosive trifluoro acetic acid solvent.
`
`Overall, the invention makes the commercial manufacture of
`
`the
`
`important insecticide Fipronil more process friendly
`
`20
`
`and economically viable.
`
`DESCRIPTION OF THE INVENTION
`
`The present invention relates to improved oxidation process
`
`25
`
`for
`
`preparing
`
`5-amino-1-phenyl-3-cyano-4-trifluoromethyl
`
`2
`
`

`
`wo 2007/122440
`
`PCT /IB2006/000999
`
`sulphinyl pyrazole pesticides as defined by
`
`formula-I
`
`below.
`
`(Formula-I)
`
`Wherein,
`
`5 Rl = trifluoromethyl or trifluoromethoxy
`
`R2, R3 = individually hydrogen, chlorine or bromine
`
`which process comprises the step of oxidizing a compound of
`
`formula-II.
`
`Rl
`
`(Formula-II)
`
`10 Wherein,
`
`Rl = trifluoromethyl or trifluoromethoxy
`
`R2, R3 = individually hydrogen, chlorine or bromine
`
`3
`
`

`
`wo 2007/122440
`
`PCT /IB2006/000999
`
`by using a medium comprising at least one oxidizing agent
`
`and trichloro acetic acid, and/or the reaction product (s)
`
`of the at least one oxidizing agent and trichloro acetic
`
`acid,
`
`and at
`
`least one melting point depressant. The
`
`5 presence of trifluoro acetic acid (TFA) is thereby rendered
`
`unnecessary. The preferred oxidizing agents are per acids,
`
`peroxides and persulfates. More preferred are peroxides, in
`
`particular benzoyl peroxide, sodium peroxide, tert butyl
`
`peroxide
`
`and
`
`hydrogen peroxide,
`
`the most preferred
`
`10
`
`oxidizing agent being hydrogen peroxide. Hydrogen peroxide
`
`may be used in the form of a concentrated aqueous solution
`
`such as those that are available commercially.
`
`European patent No. 295117 describes the preparation of
`
`15
`
`compounds of formula-I using 3-chloroperbenzoic acid, but
`
`not using the oxidation route of the present invention.
`
`WO 01
`
`I 30760 describes a process for the oxidation of
`
`compounds of formula-II
`
`to compounds of formula-I
`
`in a
`
`20
`
`trifluoro acetic acid medium using a corrosion inhibitor as
`
`an improvement to take care of the acidity generated due to
`
`the
`
`liberation of hydrofluoric acid
`
`(HF)
`
`during
`
`the
`
`reaction.
`
`25 Oxidation of compounds of the type of formula-II entails
`
`several difficulties, for example that the molecule has to
`
`4
`
`

`
`wo 2007/122440
`
`PCT /IB2006/000999
`
`be stable under the conditions of oxidation, the oxidation
`
`should proceed
`
`to
`
`the desired
`
`level without
`
`leaving
`
`significant starting materials unreacted and the oxidation
`
`should not produce
`
`an
`
`excessive
`
`level of
`
`sulfonyl
`
`5 derivative. Oxidants such as per acids, peroxides,
`
`and
`
`persulfates have been widely used for performing such
`
`oxidation reactions.
`
`The oxidation reaction is conventionally carried out in
`
`10
`
`organic
`
`solvents, particularly halogenated aliphatics,
`
`trifluoroacetic acid. Mineral acids are generally not
`
`useful as a medium for oxidation due to the instability of
`
`the compounds of
`
`the
`
`invention
`
`towards strong mineral
`
`acids.
`
`15
`
`Trifluoro acetic acid has been reported to be a good medium
`
`for effecting
`
`the oxidation, with good conversion and
`
`selectivity to the sulphinyl derivative with minimum levels
`
`of
`
`sulphonyl derivative
`
`formation. However,
`
`trichloro
`
`20
`
`acetic acid has not been reported as a medium due to its
`
`high melting point.
`
`DETAILED DESCRIPTION OF THE INVENTION
`
`25
`
`Several process problems are encountered when trifluoro
`
`acetic acid (TFA) is used as a solvent. One major problem
`
`5
`
`

`
`wo 2007/122440
`
`PCT /IB2006/000999
`
`is the corrosion of metal or glass equipment due to the
`
`liberation of HF during
`
`the reaction. WO
`
`01
`
`/
`
`30760
`
`describes how the addition of corrosion inhibiting agents
`
`such as boric acid can be used to prevent this. Whilst this
`
`5 may be effective during oxidation, since TFA is a costly
`
`chemical it needs to be recovered due to process economics.
`
`The
`
`same patent application discloses
`
`the addition of
`
`monochloro benzene
`
`and distillation of TFA. Further,
`
`residual TFA is esterified using alcohol and recovered as
`
`10
`
`an ester which needs to be converted back to TFA. Moreover,
`
`the TFA is distilled out as an azeotrope with water and
`
`separation of pure TFA
`
`from water requires distillation
`
`with sulfuric acid addition. This again poses
`
`severe
`
`corrosion problems to the equipment used. In short, the use
`
`15
`
`of TFA makes
`
`the commercial operation of
`
`the process
`
`extremely difficult and expensive.
`
`Our research has now
`
`led to a solution to this knotty
`
`problem and has made
`
`the process simple and economical.
`
`20 Our search for a substitute for TFA led to the present
`
`invention of using trichloro acetic acid.
`
`The process of
`
`the present
`
`invention
`
`involves
`
`the
`
`preparation of
`
`a
`
`compound of
`
`formula-I by
`
`a process
`
`25
`
`comprising the step of oxidizing a compound of formula-II.
`
`The oxidation is carried out in a medium comprising at
`
`6
`
`

`
`wo 2007/122440
`
`PCT /IB2006/000999
`
`least one oxidizing agent and trichloro acetic acid, and/o~
`
`the reaction product(s) of the at least one oxidizing agent
`
`and trichloro acetic acid, and at least one melting point
`
`depressant.
`
`5
`
`Since trichloro acetic acid is a solid under the conditions
`
`of oxidation, at least one melting point depressant is
`
`required. Preferred melting point depressants are dichloro
`
`acetic acid, monochloro acetic acid, methylene dichloride,
`
`10
`
`ethylene dichloride, monochlorobenzene or a haloalkane, or
`
`a mixture thereof. Trichloro acetic acid is commercially
`
`available at about one tenth the cost of Trifl uoro acetic
`
`acid and is devoid of the corrosion problems arising due to
`
`HF. The use of corrosion inhibitors such as boric acid and
`
`15
`
`the consequential processing problems that they create are
`
`therefore avoided. The present invention seeks to provide
`
`an
`
`industrial process
`
`for manufacturing
`
`compounds of
`
`formula-I, particularly Fipronil, in high yield and purity
`
`with cheaper and less corrosive chemicals.
`
`20
`
`25
`
`Furthermore,
`
`the present
`
`invention seeks
`
`to provide a
`
`process
`
`for manufacturing
`
`the
`
`compounds of
`
`formula-I,
`
`particularly Fipronil, using chemicals which do not corrode
`
`the equipment used.
`
`7
`
`

`
`wo 2007/122440
`
`PCT /IB2006/000999
`
`The preferred oxidizing agents are per acids/ peroxides and
`
`persulfates 1 with peroxides being particularly preferred.
`
`The preferred peroxides are benzoyl peroxide 1
`
`sodium
`
`peroxide/ hydrogen peroxide and tert butyl peroxide.
`
`The
`
`5
`
`preferred per acid is per acetic acid.
`
`The most preferred
`
`oxidizing agent is hydrogen peroxide.
`
`The quantity of the oxidizing agent used is sufficient to
`
`effect optimal conversion of the compound of formula-II to
`
`10
`
`the compound of formula-I without producing significant
`
`amounts of
`
`the byproduct sulphonyl derivative. For
`
`the
`
`peroxides such as hydrogen peroxide this is preferably in
`
`the range of 1.1 to 1. 7 moles 1 and more preferably about
`
`1. 4 mole 1 per mole of
`
`the compound of formula- II. The
`
`15
`
`preferred concentration of the hydrogen peroxide used is 50
`
`to 70% by weight as an aqueous solution due
`
`to
`
`the
`
`commercial availability of such solutions. Concentrations
`
`outside
`
`this
`
`range
`
`can also be used with
`
`suitable
`
`adjustments to the water concentration.
`
`20
`
`In a preferred embodiment of the process 1
`
`trichloro per
`
`acetic acid 1 which is the reactive species 1
`
`is formed
`
`'in
`
`situ 1 by contacting hydrogen peroxide with trichloro acetic
`
`acid. Other oxidizing agents such as tert butyl hydrogen
`
`25
`
`peroxide and per acetic acid can also be used 1 but with no
`
`particular advantage. For
`
`those
`
`skilled
`
`in
`
`the art 1
`
`8
`
`

`
`wo 2007/122440
`
`PCT /IB2006/000999
`
`Trichloro per acetic acid can be pre-made and used, but
`
`there is no particular advantage in doing so.
`
`The temperature for the reaction is chosen so as to give
`
`5
`
`reasonable kinetics for oxidation without decomposing the
`
`product. The
`
`reaction
`
`is preferably carried out at a
`
`temperature in the range 0°C to 50°C, more preferably in
`
`the range 15 to 25°C and most preferably at about 20°C.
`
`10 The quantity of trichloro acetic acid used should generally
`
`be sufficient
`
`to dissolve
`
`the substrate and allow
`
`the
`
`slurry of
`
`the
`
`reaction mass
`
`to be stirred properly.
`
`Preferably 1. 0 lt to 2. 0 lt of trichloro acetic acid is
`
`used per mole of
`
`the
`
`compound of
`
`formula-II.
`
`The
`
`15
`
`composition of the mixture is chosen so as to depress the
`
`melting point of the reaction medium sufficiently, usually
`
`to less than 10°C. For example, the preferred melting point
`
`depressant dichloro acetic acid
`
`is a poor medium
`
`for
`
`oxidation and
`
`the purpose of its addition is only
`
`to
`
`20
`
`sufficiently depress the melting point of trichloro acetic
`
`acid to facilitate ease of processing. 2 0-3 0% by weight
`
`content of dichloro acetic acid in the trichloro acetic
`
`acid is generally sufficient to achieve this objective. It
`
`is preferred to depress the melting point of the trichloro
`
`25
`
`acetic acid to below 10°C.
`
`9
`
`

`
`wo 2007/122440
`
`PCT /IB2006/000999
`
`In a preferred embodiment of the process of the present
`
`invention R1 =
`
`trifluoromethyl and R2, R3 = chlorine, the
`
`process therefore resulting in the production of 5-amino-1-
`
`(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-
`
`5
`
`trifluoromethyl sulphinyl pyrazole (Fipronil) .
`
`The following examples, which are non-limiting, illustrate
`
`the invention:
`
`10 Example l
`
`1000 ml of a solvent mixture, containing 700 ml trichloro
`
`acetic acid and 300 ml dichloro acetic acid, was added to a
`
`flask and 421 g
`
`(1 g mole) of 5-amino-1- (2, 6-dichloro-4-
`
`trifluoromethylphenyl)-3-cyano-4-trifluoromethyl
`
`thio
`
`15
`
`pyrazole was dissolved in it. After stirring for one hour
`
`at 20°C,
`
`95
`
`g hydrogen peroxide solution
`
`(50% w/w),
`
`equivalent to 1. 4 mole, was added over a period of one
`
`hour. As
`
`the
`
`reaction proceeded,
`
`the
`
`solid product
`
`precipitated out from the reaction mass. The reaction was
`
`20
`
`continued until
`
`the conversion was more
`
`than
`
`95%
`
`as
`
`measured by HPLC. To the reaction mass, 2 litres of water
`
`was added, stirred and filtered. The water washed solids
`
`were dried in an oven at 110°C, resulting in 415 g solids
`
`(95% yield) . HPLC determination by an internal standard
`
`25 method showed the solid to be 92% pure.
`
`10
`
`

`
`wo 2007/122440
`
`PCT /IB2006/000999
`
`The filtrate portion was processed by distillation
`
`to
`
`recover
`
`the
`
`trichloro acetic acid using a conventional
`
`method and the trichloro acetic acid was recycled.
`
`5 Example 2
`
`1500 g of trichloro acetic acid solid was added to 300 ml
`
`of methylene dichloride. To this solution at 20°C, 421 g
`
`(1
`
`g
`
`mole)
`
`of
`
`5-amino-1-(2,6-dichloro-4-
`
`trifluoromethylphenyl)-3-cyano-4-trifluoromethyl
`
`thio
`
`10
`
`pyrazole was added and allowed to dissolve. After stirring
`
`for 1 hour at 20°C, 93 g hydrogen peroxide solution (50%
`
`w/w), equivalent to 1.36 g mole, was added over a period of
`
`2 hrs. The reaction was continued until the conversion was
`
`>95% using an HPLC area method. The excess hydrogen
`
`15
`
`peroxide was destroyed using Na 2803
`
`and
`
`the
`
`sol vent
`
`methylene dichloride was distilled out under a mild vacuum.
`
`To
`
`the residual mass, 2. 0 1 t water was added and
`
`the
`
`precipitated solids were filtered resulting in 410 g of
`
`buff coloured solids
`
`(yield
`
`93.8%). The solids were
`
`20
`
`analyzed by an HPLC internal standard method and were found
`
`to be 92% pure.
`
`11
`
`

`
`wo 2007/122440
`CLAIMS:
`
`PCT /IB2006/000999
`
`1.
`
`A process for the preparation of 5-amino-1-phenyl-3-
`
`cyano-4-trifluoromethyl sulphinyl pyrazoles as defined by
`
`5 Formula-I,
`
`(Formula-I)
`
`wherein: R1 = trifluoromethyl or trifluoromethoxy, and
`
`R2, R3 =
`
`individually hydrogen,
`
`chlorine or
`
`bromine,
`
`10
`
`the process comprising the step of oxidizing a compound of
`
`Formula-II,
`
`Rl
`
`(Formula-II)
`
`wherein: R1 = trifluoromethyl or trifluoromethoxy, and
`
`12
`
`

`
`wo 2007/122440
`
`bromine,
`
`R2, R3 =
`
`individually hydrogen,
`
`chlorine or
`
`PCT /IB2006/000999
`
`in a medium comprising at least one oxidizing agent and
`
`trichloro acetic acid, and/or the reactions product (s) of
`
`5
`
`the at least one oxidizing agent and trichloro acetic acid,
`
`and at least one melting point depressant.
`
`2.
`
`A process as claimed in claim 1, wherein the at least
`
`one oxidizing agent
`
`is a per acid,
`
`a peroxide or a
`
`10 persulfate.
`
`3.
`
`A process as claimed in claim 2, wherein the peroxide
`
`is hydrogen peroxide, tert butyl hydrogen peroxide, benzoyl
`
`peroxide or sodium peroxide.
`
`15
`
`4.
`
`A process as claimed in claim 3, wherein the hydrogen
`
`peroxide is used in an amount of between 1.1 and 1.7 moles
`
`per mole of the compound of formula-II.
`
`20
`
`5 .
`
`A process as claimed in claim 4, wherein the hydrogen
`
`peroxide is used in an amount of about 1.4 moles per mole
`
`of the compound of formula-II.
`
`6.
`
`A process as claimed in any one of claims 3
`
`to 5,
`
`25 wherein
`
`the hydrogen peroxide is added as a 50-70% by
`
`weight aqueous solution.
`
`13
`
`

`
`wo 2007/122440
`
`PCT /IB2006/000999
`
`7.
`
`A process as claimed in claim 2, wherein the per acid
`
`is per acetic acid.
`
`5
`
`8 .
`
`A process as claimed in any one of
`
`the preceding
`
`claims, wherein the at least one melting point depressant
`
`is monochloro acetic acid, dichloro acetic acid, methylene
`
`dichloride, ethylene dichloride, monochlorobenzene or a
`
`haloalkane.
`
`10
`
`9.
`
`A process as claimed in claim 8, wherein the dichloro
`
`acetic acid is used in an amount of between 20% and 30%
`
`either w/w or v/v in the trichloroacetic acid.
`
`15
`
`10. A process as claimed in any one of
`
`the preceding
`
`claims, wherein the process is carried out at a temperature
`
`in the range 0-50°C.
`
`11. A process as claimed in claim 10, wherein the process
`
`20
`
`is carried out at a temperature in the range 15-25°C.
`
`12. A process as claimed in claim 11, wherein the process
`
`is carried out at a temperature of about 20°C.
`
`25
`
`13 . A process as claimed in any one of
`
`the preceding
`
`claims, wherein the at least one melting point depressant
`
`14
`
`

`
`wo 2007/122440
`
`PCT /IB2006/000999
`
`is used in such an amount as to depress the melting point
`
`of the reaction medium to less than 10°C.
`
`14. A process as claimed in any one of
`
`the preceding
`
`5
`
`claims, wherein the trichloro acetic acid is used in an
`
`amount of between 1.0 litres and 2.0 litres per mole of the
`
`compound of formula-II.
`
`15. A process as claimed in any one of
`
`the preceding
`
`10
`
`claims, wherein R1 = trifluoromethyl and R2, R3 = chlorine.
`
`15
`
`

`
`INTERNATIONAL SEARCH REPORT
`
`International application No
`PCT/IB2006/000999
`
`A. CLASSIFICATION OftUBJECT MATTER
`INV. C07D231 44
`
`According to International Patent Classification (lPG) or to both national classification and lPG
`
`B. FIELDS SEARCHED
`Minimum documentation searched (classification system followed by classification symbols)
`C07D
`
`Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched
`
`Electronic data base consulted during the international search (name of data base and, where practical, search terms used)
`EPO-Internal, BEILSTEIN Data, CHEM ABS Data
`
`C. DOCUMENTS CONSIDERED TO BE RELEVANT
`
`Category*
`
`C~ation of document, with indication, where appropriate, of the relevant passages
`
`Relevant to claim No.
`
`A
`
`A
`
`BARTON D. H. R. ET AL.:
`TETRAHEDRON LETT.,
`vol. 23, no. 9, 1982, pages 957-960,
`XP002417809
`tables 1,2
`-----
`wo 01/30760 A (AVENTIS CROPSCIENCE SA
`[FR]; CLAVEL JEAN LOUIS [FR]; PELTA
`ISABELLE [F) 3 May 2001 (2001-05-03)
`cited in the application
`the whole document
`-----
`
`1-15
`
`1-15
`
`D Further documents are listed in the continuation of Box C.
`
`• Special categories of cited documents :
`
`• A' document defining the general state of the art which is not
`considered to be of particular relevance
`'E' earlier document but published on or after the international
`filing date
`'L' document which may throw doubts on priority claim(s) or
`which is cited to establish the publication date of another
`citation or other special reason (as specified)
`'0' document referring to an oral disclosure, use, exhibition or
`other means
`•p• document published prior to the international filing date but
`later than the priority date claimed
`
`[] See patent family annex.
`
`'T' later document published after the international filing date
`or priority date and not in conflict with the application but
`cited to understand the principle or theory underlying the
`invention
`•x• document of particular relevance; the claimed invention
`cannot be considered novel or cannot be considered to
`involve an inventive step when the document is taken alone
`•y• document of particular relevance; the claimed invention
`cannot be considered to involve an inventive step when the
`document is combined with one or more other such docu-
`ments, such combination being obvious to a person skilled
`in the art.
`'&' document member of the same patent family
`
`Date of the actual completion of the international search
`
`Date of mailing of the international search report
`
`1 February 2007
`
`Name and mailing address of the ISN
`European Patent Office, P.B. 5818 Patenllaan 2
`NL - 2280 HV Rijswijk
`Tel. (+31-70) 340-2040, Tx. 31 651 epo nl,
`Fax: (+31-70)340-3016
`
`Form PCT/ISN210 (second sheet) (Apnl2005)
`
`28/02/2007
`
`Authorized officer
`
`Grassi, Damian
`
`

`
`INTERNATIONAL SEARCH REPORT
`Information on patent family members
`
`International application No
`PCT/182006/000999
`
`Patent document
`cited in search report
`
`Publication
`date
`
`Patent family
`member(s)
`
`I Publication
`
`date
`
`wo 0130760
`
`A
`
`03-05-2001
`
`AT
`273961 T
`15-09-2004
`AU
`783139 82
`29-09-2005
`AU
`1270700 A
`08-05-2001
`BG
`106622 A
`29-12-2002
`CA
`2384283 A1
`03-05-2001
`CN
`1332730 A
`23-01-2002
`cz
`20021384 A3
`14-08-2002
`DE
`69919599 01
`23-09-2004
`DE
`69919599 T2
`11-08-2005
`EA
`5077 81
`28-10-2004
`EP
`1222173 A1
`17-07-2002
`ES
`2222743 T3
`01-02-2005
`HU
`0203206 A2
`28-03-2003
`JP
`2003512456 T
`02-04-2003
`MX
`PA02003944 A
`15-10-2003
`PT
`1222173 T
`30-11-2004
`TR
`200202806 T2
`21-03-2003
`TW
`553936 B
`21-09-2003
`UA
`73752 C2
`15-08-2002
`us
`6620943 81
`16-09-2003
`-----------------------------------------------------------------------
`
`Form PGT/ISN21 o (patent famtly annex) (April2005)