Process for the preparation of 5-fluoro-1H-pyrazoles starting from hexafluoropropene

Patent metadata

Field	Value
Publication number	US-10059673-B2
Application number	US-201515504294-A
Country	US
Kind code	B2
Filing date	Aug 14, 2015
Priority date	Aug 19, 2014
Publication date	Aug 28, 2018
Grant date	Aug 28, 2018

Abstract

A new process for the preparation of 5-fluoro-1H-pyrazoles of the general formula (I) as described herein and further reactions with this compound.

First claim

The invention claimed is:

1. Process for the synthesis of 5-fluoro-1H-pyrazole of formula (I)

wherein R 1 represents (C 1 -C 4 )-alkyl;
comprising
reacting intermediate (3) with (C 1 -C 4 )-alkyl-CONHNH 2 to prepare 3-perfluoroethyl-4-perfluoromethyl-5-fluoro-pyrazol (intermediate (4))

 and
reacting intermediate (4) with an (C 1 -C 4 )-alkylation agent, optionally a methylation agent to prepare a compound of formula (I) (step 4).

2. Process for the synthesis of 5-fluoro-1H-pyrazole of formula (I) according to claim 1 comprising
Reacting hexafluoropropene (intermediate (1))

in the presence of a catalyst to form its dimer perfluoro-4-methyl-2-pentene (intermediate (2))

 and
isomerizing perfluoro-4-methyl-2-pentene into perfluoro-2-methyl-2-pentene (intermediate (3))

 and
reacting a compound (3) with (C 1 -C 4 )-alkyl-CONHNH 2 to prepare 3-perfluoroethyl-4-perfluoromethyl-5-fluoro-pyrazol (intermediate (4))

 and
reacting intermediate (4) with an (C 1 -C 4 )-alkylation agent, optionally a methylation agent, to prepare a compound of formula (I).

3. Process for the preparation of a compound of formula (IV)

in which
R 1 is C 1 -C 4 -alkyl; and
A 1 is C—R 2 ; and
R 2 is hydrogen, fluorine, chlorine, bromine, CN, NO 2 , optionally halogenated C 1 -C 6 -alkyl, optionally halogenated C 1 -C 4 -alkoxy, optionally halogenated C 1 -C 4 -alkylsulphonyl, optionally halogenated C 1 -C 4 -alkylsulphinyl or N-cyclopropylaminocarbonyl (—C(═O)NH—cyclopropyl); preferably hydrogen, fluorine, chlorine, bromine, CN, NO 2 , methyl, ethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, methoxy, ethoxy, n-propoxy, 1-methylethoxy, fluoromethoxy, difluoromethoxy, chlorodifluoromethoxy, dichlorofluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2,2-difluoroethoxy, pentafluoroethoxy, methylsulphonyl, methylsulphinyl, trifluoromethylsulphonyl, trifluoromethylsulphinyl or N-cyclopropylaminocarbonyl, more preferably hydrogen, fluorine, chlorine, bromine, CN, NO 2 , methyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, methoxy, ethoxy, or pentafluoroethoxy, optionally hydrogen, fluorine, chlorine, bromine, most preferably chlorine; and
A 2 is C—R 3 or nitrogen; and
R 3 is hydrogen, methyl, fluorine or chlorine, optionally hydrogen; and
T represents one of the groups T1-T9 listed below, where the bond to the pyrazole head group is marked with an asterisk *,

 and
R 6 independently of one another represents halogen, cyano, nitro, amino or optionally substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkyloxy, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkylsulphanyl, C 1 -C 6 -alkylsulphinyl, C 1 -C 6 -alkylsulphonyl, and
n represents the values 0-2, optionally 0, provided that n is 0 or 1 in T5, T6 and T8 and provided n is 0 in T7; and
Q is hydrogen, cyano, hydroxy, formyl or one of the groupings C 1 -C 6 -alkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl, C 3 -C 9 -cycloalkyl, C 3 -C 9 -heterocycloalkyl, C 1 -C 4 -alkoxy, C 4 -C 15 -alkylcycloalkyl, C 4 -C 15 -cycloalkylalkyl, C 1 -C 6 -hydroxyalkyl, C 6 -aryl-C 1 -C 3 -alkyl, C 5 -C 6 -heteroaryl-C 1 -C 3 -alkyl, C 1 -C 4 -aminoalkyl, aminocarbonyl-C 1 -C 4 -alkyl or C 1 -C 4 -alkyl-amino-C 1 -C 4 -alkyl which are optionally substituted with one, two, three, four or five, optionally with one or two, optionally with one, substituents independently selected from the group consisting of hydroxy, nitro, amino, halogen, C 1 -C 3 -alkoxy, cyano, hydroxycarbonyl, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkylcarbamoyl, C 4 -C 6 -cycloalkylcarbamoyl and optionally independently with one, two or three substituents selected from the group consisting of halogen, cyano, nitro, hydroxycarbonyl, C 1 -C 2 -alkylcarbamoyl, C 1 -C 2 -alkyl, halogenated C 1 -C 2 -alkyl and C 1 -C 2 -alkoxy substituted phenyl; preferably Q is C 3 -C 6 -cycloalkyl, or C 3 -C 6 -cycloalkyl which is substituted with at least one substituent selected from the group consisting of chlorine, fluorine, bromine, iodine, cyano and hydroxy, or C 6 -aryl-C 1 -C 3 -alkyl; more preferably cyclopropyl, 1-cyano-cyclopropyl or benzyl (—CH 2 —C 6 H 5 );
Comprising the process according to claim 1 .

4. Process according to claim 3 , wherein a compound of formula (IV) is a compound of formula (II)

optionally of formula (II′)

5. Process according to claim 3 , wherein a compound of formula (IV) is compound (IIa)

6. Process according to claim 3 , further comprising:
reacting compound (I) with a cyano-donor to prepare intermediate of formula (6)

wherein R 1 is (C 1 -C 4 )-alkyl; and
reacting compound (6) with an inorganic strong base in a first hydrolysis step followed by adding an inorganic acid in a second hydrolysis step to prepare intermediate of formula (7)

wherein
R 1 is (C 1 -C 4 )-alkyl; and
reacting a compound of formula (8) or its salt (8′) with an activated form (7′) of compound (7)

wherein R 1 , A 1 , A 2 , and Q are as defined in claim 3 and LG is any leaving group, to prepare a compound of formula (II).

7. Process according to claim 3 , wherein a compound of formula (IV) is a compound of formula (III)

in which
R 1 is (C 1 -C 4 )-alkyl; and
A 1 is C—R 2 ;
R 2 is hydrogen, fluorine, chlorine, bromine, CN, NO 2 , optionally halogenated C 1 -C 6 -alkyl, optionally halogenated C 1 -C 4 -alkoxy, optionally halogenated C 1 -C 4 -alkylsulphonyl, optionally halogenated C 1 -C 4 -alkylsulphinyl or N-cyclopropylaminocarbonyl (—C(═O)—NH—cyclopropyl); optionally hydrogen, fluorine, chlorine, bromine, CN, NO 2 , methyl, ethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, methoxy, ethoxy, n-propoxy, 1-methylethoxy, fluoromethoxy, difluoromethoxy, chlorodifluoromethoxy, dichlorofluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2,2-difluoroethoxy, pentafluoroethoxy, methylsulphonyl, methylsulphinyl, trifluoromethylsulphonyl, trifluoromethylsulphinyl or N-cyclopropylaminocarbonyl, optionally hydrogen,

Assignees

• Bayer Cropscience Ag

Inventors

• Pazenok Sergii

Classifications

• C07D231/16 Primary

  Halogen atoms or nitro radicals · CPC title

• C07D403/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07C17/358

  by isomerisation · CPC title

• C07D231/14

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title

• C07D231/12

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title