Process for preparing 3-fluoroalkyl-5-pyrazolecarboxylates and 3-fluoroalkyl-5-pyrazolecarboxylic acids

Patent metadata

Field	Value
Publication number	US-10556867-B2
Application number	US-201716335138-A
Country	US
Kind code	B2
Filing date	Sep 18, 2017
Priority date	Sep 21, 2016
Publication date	Feb 11, 2020
Grant date	Feb 11, 2020

Abstract

The present invention relates to a novel process for preparing 3-fluoroalkyl-5-pyrazolecarboxylates from ketimines and oxalic acid derivatives which can be further transformed into 3-fluoroalkyl-5-pyrazolecarboxylic acids.

First claim

The invention claimed is:

1. A process for preparing a 3-fluoroalkyl-5-pyrazolecarboxylate of formula (I),

in which
R 1 is C 1 -C 6 -haloalkyl;
R 2 is selected from the group consisting of C 1-12 -alkyl, C 3-8 -cycloalkyl, C 6-18 -aryl, and C 7-18 -arylalkyl-;
R 3 is selected from the group consisting of H, C 1 -C 12 alkyl, benzyl, phenyl, C 6-18 -aryl, and pyridyl;
the process comprising:
in step (A), reacting an oxalic acid derivative of formula (II),

in which
R 2 is as defined above;
X is F, Cl or Br;
with a compound of formula (III),

in which
R 4 is selected from the group consisting of C 1-12 -alkyl, C 3-8 -cycloalkyl, benzyl, and C 7-18 -arylalkyl-;
R 1 is as defined above;
in the presence of a base to form a compound of formula (IV)

in which
R 1 , R 2 , R 4 are as defined above; and
in step (B), reacting the compound of formula (IV) with a hydrazine of formula H 2 N—NHR 3 (III)
in which R 3 is as defined above;
and an acid to form the 3-fluoroalkyl-5-pyrazolecarboxylate of formula (I).

2. The process according to claim 1 , wherein:
R 1 is selected from the group consisting of difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, tetrafluoroethyl (CF 3 CFH), pentafluoroethyl, and 1,1,1-trifluoroprop-2-yl;
R 2 is selected from the group consisting of methyl, ethyl, propyl and t-butyl, benzyl, and phenylethyl-;
R 3 is selected from the group consisting of H, C 1 -C 8 alkyl, aryl, benzyl and pyridyl;
R 4 is selected from the group consisting of methyl, ethyl, n-, iso-propyl, n-, iso-, sec-und t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, and phenylethyl-; and
X is F or Cl.

3. The process according to claim 1 , wherein:
R 1 is selected from the group consisting of trifluoromethyl, difluoromethyl, difluorochloromethyl, and pentafluoroethyl;
R 2 is selected from the group consisting of methyl and ethyl;
R 3 is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, butyl, pentyl, benzyl, and phenyl;
R 4 is selected from the group consisting of benzyl and iso-propyl;
X is Cl.

4. The process according to claim 1 , wherein:
R 1 is difluoromethyl, difluorochloromethyl or trifluoromethyl;
R 2 is methyl or ethyl;
R 3 is selected from the group consisting of H, methyl, ethyl, benzyl, and phenyl;
R 4 is iso-propyl or benzyl; and
X is Cl.

5. The process according to claim 1 , wherein:
R 1 is difluoromethyl or trifluoromethyl;
R 2 is methyl or ethyl;
R 3 is selected from the group consisting of H, methyl, and phenyl;
R 4 is benzyl; and
X is Cl.

6. The process according to claim 1 ,
wherein the base in step (A) is selected from the group consisting of pyridine, 3-methylpyridine, and ethyldiisopropylamine.

7. The process according to claim 1 ,
wherein the acid in step (B) is selected from the group consisting of H 2 SO 4 , HCl, HF, HBr, HI, H 3 PO 4 , CH 3 COOH, CF 3 COOH, p-toluenesulphonic acid, methanesulphonic acid, and trifluoromethanesulphonic acid.

8. A process for preparing a 3-fluoroalkyl-5-pyrazole acid, of formula (VI),

in which
R 1 is C 1 -C 6 -haloalkyl;
R 3 is selected from the group consisting of H, C 1 -C 12 alkyl, benzyl, phenyl, C 6-18 -aryl, and pyridyl;
comprising
(i) the process according to claim 1 , and
(ii) hydrolysing the compound of the formula (I) to form the compound of the formula (VI).

9. The process according to claim 8 , wherein the
hydrolysis reaction is performed under basic conditions.

10. A compound of formula (IV)

in which
R 1 is difluoromethyl or trifluoromethyl;
R 2 is methyl or ethyl; and
R 4 is iso-propyl or benzyl.

11. The process according to claim 9 , wherein the basic conditions comprise the
presence of a base selected from the group consisting of NaOH, KOH, Na 2 CO 3 , and K 2 CO 3 .

Assignees

• Bayer Cropscience Ag
• Centre Nat Rech Scient

Inventors

• Pazenok Sergii
• Vors Jean-Pierre
• Leroux Frédéric R
• Schmitt Etienne

Classifications

• C07D231/14 Primary

  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

• C07D251/08 Primary

  having one double bond between ring members or between a ring member and a non-ring member · CPC title

• C07C249/02

  of compounds containing imino groups · CPC title

• C07D401/04

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

• C07C251/08

  being acyclic · CPC title