Process for preparing cis-alkoxy-substituted spirocyclic phenylacetylamino acid esters and cis- alkoxy-substituted spirocyclic 1H- pyrrolidine-2,4-dione derivatives

Patent metadata

Field	Value
Publication number	US-9376374-B2
Application number	US-201314387249-A
Country	US
Kind code	B2
Filing date	Mar 25, 2013
Priority date	Mar 28, 2012
Publication date	Jun 28, 2016
Grant date	Jun 28, 2016

Abstract

The present invention relates to a novel process for preparing cis-alkoxy-substituted spirocyclic phenylacetylamino acid esters and cis-alkoxy-substituted spirocyclic 1H-pyrrolidine-2,4-dione derivatives, and also to novel intermediates and starting materials which are produced and/or used in the process according to the invention.

First claim

The invention claimed is:

1. Process for preparing a compound of formula (I)

in which
X represents alkyl, halogen, alkoxy, haloalkyl or haloalkoxy,
Y represents hydrogen, alkyl, alkoxy, halogen, haloalkyl or haloalkoxy, where only one of the radicals X or Y may represent haloalkyl or haloalkoxy,
A represents C 1 -C 6 -alkyl,
R′ represents alkyl,
R″ represents alkyl,
comprising initially converting a compound of formula (IIa)

in the presence of a base into a compound of formula (IIb)

in which
M represents 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 furthermore represents an ammonium ion where optionally one, two, three or all four hydrogen atoms may 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, each of which may be mono- or polysubstituted by fluorine, chlorine, bromine, cyano, hydroxy or interrupted by one or more oxygen or sulphur atoms, or furthermore
represents a cyclic secondary or tertiary aliphatic or heteroaliphatic ammonium ion, for example morpholinium, thiomorpholinium, piperidinium, pyrrolidinium, or in each case protonated 1,4-diazabicyclo[2.2.2]octane (DABCO) or 1,5-diazabicyclo[4.3.0]undec-7-ene (DBU), or furthermore
represents a heterocyclic ammonium cation, for example in each case protonated pyridine, 2-methylpyridine, 3-methylpyridine, 4-methylpyridine, 2,4-dimethylpyridine, 2,5-di-methylpyridine, 2,6-dimethylpyridine, 5-ethyl-2-methylpyridine, pyrrole, imidazole, quinoline, quinoxaline, 1,2-dimethylimidazole, 1,3-dimethylimidazolium methylsulphate, or furthermore
represents a sulphonium ion, or furthermore
represents a magnesium halide cation,

n represents the number 1 or 2,
and reacted further with a compound of formula (III)

in which
Hal represents halogen,
to give a compound of formula (IV)

in which X, Y, A and R′ have the meanings given above,
and
these are further cyclized to a compound of formula (IX)

in which X, Y and A have the meanings given above,
and these for their part are reacted with a compound of formula (V)
R″—OH  (V)

in which R″ has the meanings given above.

2. Process according to claim 1 , where
X represents chlorine, bromine, methyl, ethyl, propyl, trifluoromethyl, methoxy, difluoromethoxy or trifluoromethoxy,
Y represents hydrogen, chlorine, bromine, methoxy, methyl, ethyl, propyl, trifluoromethyl or trifluoromethoxy, where only one of the radicals X or Y may represent trifluoromethyl, trifluoromethoxy or difluoromethoxy,
A represents C 1 -C 6 -alkyl,
Hal represents chlorine, bromine, fluorine, iodine,
R′ represents C 1 -C 6 -alkyl,
R″ represents C 1 -C 6 -alkyl.

3. Process according to claim 1 , where
X represents chlorine, bromine, methyl, ethyl, methoxy, trifluoromethyl, trifluoromethoxy or difluoromethoxy,
Y represents chlorine, bromine, methyl, ethyl, propyl, methoxy, trifluoromethyl or trifluoromethoxy, where only one of the radicals X or Y may represent trifluoromethyl, trifluoromethoxy or difluoromethoxy,
A represents C 1 -C 4 -alkyl,
Hal represents chlorine, bromine or fluorine,
R′ represents C 1 -C 4 -alkyl,
R″ represents C 1 -C 4 -alkyl.

4. Process according to claim 1 , where
X represents chlorine, bromine, methyl or trifluoromethyl,
Y represents chlorine, bromine or methyl,
A represents methyl, ethyl, propyl, butyl or isobutyl,
Hal represents chlorine or bromine,
R′ represents methyl, ethyl, propyl, butyl or isobutyl,
R″ represents methyl, ethyl, propyl, butyl or isobutyl.

5. Process according to claim 1 , where
X represents methyl,
Y represents methyl,
A represents methyl,
Hal represents chlorine,
R′ represents methyl or ethyl,
R″ represents methyl or ethyl.

6. Process according to claim 1 , where
X represents methyl,
Y represents methyl,
A represents methyl,
Hal represents chlorine,
R′ represents ethyl,
R″ represents methyl.

7. Process according to claim 1 , where
M represents lithium, sodium, potassium, caesium, magnesium, calcium or represents an ammonium ion in which optionally one, two, three or all four hydrogen atoms may 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, each of which may be mono- or polysubstituted by fluorine, chlorine, bromine, cyano, hydroxy and
n represents the number 1 or 2.

8. Process according to claim 1 , where
M represents lithium, sodium, potassium, caesium, magnesium or calcium and
n represents the number 1 or 2.

9. Process according to claim 1 , where
M represents lithium, sodium, potassium or caesium and
n represents the number 1.

10. Process according to claim 1 , where
M represents sodium and
n represents the number 1.

11. Process according to claim 1 , where the base employed is sodium carbonate.

12. Process according to claim 1 , where the base employed is sodium methoxide.

13. Process according to claim 1 , where the base employed is sodium hydroxide.

14. A Compound of formula (IX)

in which
X represents alkyl, halogen, alkoxy, haloalkyl or haloalkoxy,
Y represents hydrogen, alkyl, alkoxy, halogen, haloalkyl or haloalkoxy, where only one of the radicals X or Y may represent haloalkyl or haloalkoxy,
A represents C 1 -C 6 -alkyl,
R′ represents alkyl,
R″ represents alkyl,
M represents 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 furthermore
represents an ammonium ion where optionally one, two, three or all four hydrogen atoms may 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, each of which may be mono- or polysubstituted by fluorine, chlorine, bromine, cyano, hydroxy or interrupted by one or more oxygen or sulphur atoms, or furthermore
represents a cyclic secondary or tertiary aliphatic or heteroaliphatic ammonium ion, for example morpholinium, thiomorpholinium, piperidinium, pyrrolidinium, or in each case protonated 1,4-diazabicyclo[2.2.2]octane (DABCO) or 1,5-diazabicyclo[4.3.0]undec-7-ene (DBU), or furthermore
represents a heterocyclic ammonium cation, for example in each case protonated pyridine, 2-methylpyridine, 3-methylpyridine, 4-methylpyridine, 2,4-dimethylpyridine, 2,5-di-methylpyridine, 2,6-dimethylpyridine, 5-ethyl-2-methylpyridine, pyrrole, imidazole, quinoline, quinoxaline, 1,2-dimethylimidazole, 1,3-dimethylimidazolium methylsulphate, or furthermore
represents a sulphonium ion, or furthermore
represents a magnesium halide cation,

n represents

Assignees

• Bayer Ip Gmbh
• Bayer Cropscience Ag

Inventors

• Farida Taraneh
• Maiwald Berndt
• Littmann Martin
• Etzel Winfried
• Warsitz Rafael
• Henck Nicolas
• Esser Michael

Classifications

• C07D209/54

  Spiro-condensed · CPC title

• C07C2601/14

  The ring being saturated · CPC title

• C07C231/12 Primary

  by reactions not involving the formation of carboxamide groups · CPC title

• C07D263/52

  condensed with carbocyclic rings or ring systems · CPC title

• C07C233/51 Primary

  having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings · CPC title