Method for preparing cis-alkoxy-substituted spirocyclic 1-H-pyrrolidine-2,4-dione derivatives

Patent metadata

Field	Value
Publication number	US-10577320-B2
Application number	US-201716098138-A
Country	US
Kind code	B2
Filing date	Apr 26, 2017
Priority date	May 4, 2016
Publication date	Mar 3, 2020
Grant date	Mar 3, 2020

Abstract

The present invention relates to novel methods for preparing cis-alkoxy-substituted spirocyclic 1-H-pyrrolidine-2,4-dione derivatives and also to novel intermediates and starting compounds, which are passed through or used in the method according to the invention.

First claim

The invention claimed is:

1. A method for preparing a compound of formula (I)

in which
X is C 1 -C 6 -alkyl, halogen, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkyl or C 1 -C 6 -haloalkoxy,
Y is hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, halogen, C 1 -C 6 -haloalkyl or C 1 -C 6 -haloalkoxy, wherein only one of the radicals X or Y may be C 1 -C 6 -haloalkyl or C 1 -C 6 -haloalkoxy,
A is C 1 -C 6 -alkyl,
G is the group

in which
R′ is C 1 -C 20 -alkyl, C 2 -C 20 -alkenyl, C 1 -C 8 -alkoxy-C 2 -C 8 -alkyl or poly-C 1 -C 8 -alkoxy-C 2 -C 8 -alkyl, in each case optionally substituted by halogen,
is C 3 -C 8 -cycloalkyl optionally substituted by halogen, C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy or
is phenyl or benzyl in each case optionally substituted by halogen, cyano, nitro, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkyl or C 1 -C 6 -haloalkoxy,

wherein firstly a compound of formula (II)

in which X, Y and A are as defined above and
R″ is C 1 -C 6 -alkyl,
are cyclized in the presence of a base and in the presence of one or more solvents to give compound of formula (III)

in which X, Y and A are as defined above and
M is an alkali metal ion, an ion equivalent of an alkaline earth metal, an ion equivalent of aluminium or an ion equivalent of a transition metal, or further
is an ammonium ion, in which optionally one, two, three or all four hydrogen atoms can be replaced by identical or different radicals from the groups C 1 -C 5 -alkyl, C 1 -C 5 -isoalkyl or C 3 -C 7 -cycloalkyl, which can in each case be substituted one or more times with fluorine, chlorine, bromine, cyano, hydroxy or be interrupted by one or more oxygen or sulphur atoms, or further
is a cyclic secondary or tertiary aliphatic or heteroaliphatic ammonium ion, or further
is a heterocyclic ammonium cation, or further
is a sulphonium ion, or further
is a magnesium halogen cation,

m is the number 1, 2 or 3,
n is the number 1, 2 or 3
and are reacted with a compound of formula (IV)

in which
R′ is C 1 -C 6 -alkyl,
q is the number 0 or 1,
and Hal represents halogen,
optionally in the presence of one or more solvents and optionally in the presence of an acid binder and optionally in the presence of a phase transfer catalyst.

2. The method according to claim 1 , wherein
X is chlorine, bromine, methyl, ethyl, propyl, trifluoromethyl, methoxy, difluoromethoxy or trifluoromethoxy,
Y is hydrogen, chlorine, bromine, methoxy, methyl, ethyl, propyl, trifluoromethyl or trifluoromethoxy, wherein only one of the radicals X or Y may be trifluoromethyl or trifluoromethoxy,
A is C 1 -C 6 -alkyl,
Hal is chlorine, bromine, fluorine or iodine,
R′ is C 1 -C 6 -alkyl,
R″ is C 1 -C 6 -alkyl,
q is the number 0 or 1.

3. The method according to claim 1 , wherein
X is chlorine, bromine, methyl, ethyl, methoxy, trifluoromethyl, trifluoromethoxy or difluoromethoxy,
Y is chlorine, bromine, methyl, ethyl, propyl, methoxy, trifluoromethyl or trifluoromethoxy, wherein only one of the radicals X or Y may be trifluoromethyl or trifluoromethoxy,
A is C 1 -C 4 -alkyl,
Hal is chlorine, bromine or fluorine,
R′ is C 1 -C 4 -alkyl,
R″ is C 1 -C 4 -alkyl,
q is the number 0 or 1.

4. The method according to claim 1 , wherein
X is chlorine, bromine, methyl or trifluoromethyl,
Y is chlorine, bromine or methyl,
A is methyl, ethyl, propyl, butyl or isobutyl,
Hal is chlorine or bromine,
R′ is methyl, ethyl, propyl, butyl or isobutyl,
R″ is methyl, ethyl, propyl, butyl or isobutyl,
q is the number 0 or 1.

5. The method according to claim 1 , wherein
X is methyl,
Y is methyl,
A is methyl,
Hal is chlorine,
R′ is methyl or ethyl,
R″ is methyl or ethyl,
q is the number 0 or 1.

6. The method according to claim 1 , wherein
X is methyl,
Y is methyl,
A is methyl,
Hal is chlorine,
R′ is ethyl,
R″ is methyl,
q is the number 0 or 1.

7. The method according to claim 1 , wherein
M is lithium, sodium, potassium, caesium, magnesium, calcium or an ammonium ion, in which optionally one, two, three or all four hydrogen atoms can be replaced by identical or different radicals from the groups hydrogen, C 1 -C 5 -alkyl, C 1 -C 5 -isoalkyl or C 3 -C 7 -cycloalkyl, which can in each case be substituted one or more times with fluorine, chlorine, bromine, cyano, hydroxy,
m is the number 1 or 2 and n is the number 1 or 2.

8. The method according to claim 1 , wherein
M is lithium, sodium, potassium, caesium, magnesium or calcium,
m is the number 1 or 2 and n is the number 1 or 2.

9. The method according to claim 1 , wherein
M is lithium, sodium, potassium or caesium,
m is the number 1 and n is the number 1.

10. The method according to claim 1 , wherein
M is sodium,
m is the number 1 and n is the number 1.

11. The method according to claim 1 , wherein DMAC (dimethylacetamide) is used as solvent.

12. The method according to claim 1 , wherein sodium methoxide is used as base.

13. The method according to claim 1 , wherein triethylamine is used as acid binder.

14. The method according to claim 1 , wherein dimethylbenzylamine is used as acid binder.

15. The method according to claim 1 , wherein Aliquat 336 is used as phase transfer catalyst.

16. The method according to claim 1 , wherein the compound of the formula (III) formed in a redissociation of compound of the formula (I), by reaction with compound of the formula (IV) optionally in the presence of a solvent and optionally in the presence of an acid binder, are recycled to give one or more compounds of the formula (I).

17. The method according to claim 1 , wherein a non-polar solvent is used if the reaction of the compound of the formula (III) with a compound of the formula (IV) is carried out in the presence of water.

18. The method according to claim 17 , wherein xylene is used as solvent.

19. The method according to claim 17 , wherein methanol is used as cosolvent for the reaction of a compound of the formula (II) to give a compound of the formula (III).

20. The method according to claim 17 , wherein sodium methoxide is used as base.

21. The method according to claim 17 , wherein triethylamine is used as acid binder.

22. The method according to claim 17 , wherein dimethylbenzylamine is used as acid binder.

23. The method according to claim 17 , wherein Aliquat 336 is used as phase transfer catalyst.

24. The method according to claim 17 , wherein aqueous sodium hydroxide solution is used as base to adjust the pH.

25. A compound of formula (III)

in which
X is C 1 -C 6 -alky

Assignees

• Bayer Cropscience Ag

Inventors

• Farida Taraneh
• Littmann Martin
• Warsitz Rafael
• Esser Michael
• Schnatterer Albert

Classifications

• C07D201/08

  from carboxylic acids or derivatives thereof, e.g. hydroxy carboxylic acids, lactones or nitriles · CPC title

• C07D207/38 Primary

  2-Pyrrolones · CPC title

• C07D201/02 Primary

  Preparation of lactams · CPC title