Process for preparing substituted cyclohexane amino acid esters and spiroketal-substituted cyclic keto-enols

Patent metadata

Field	Value
Publication number	US-12006327-B2
Application number	US-201917046156-A
Country	US
Kind code	B2
Filing date	Apr 3, 2019
Priority date	Apr 10, 2018
Publication date	Jun 11, 2024
Grant date	Jun 11, 2024

Abstract

The present invention relates to a novel process for preparing substituted cyclohexane amino acid esters and spiroketal-substituted cyclic keto-enols, and to novel intermediates or starting compounds that are passed through or used in the process according to the invention.

First claim

The invention claimed is:

1. A process for preparing one or more compounds of formula (XI), comprising converting one or more compounds of formula (III) by reaction with one or more compounds of formula (XV)
R 7 —OH  (XV)

and thionyl chloride to give one or more mixtures of one or more hydrochlorides of one or more compounds of formulae (IV′), (V′) and (VI′), said one or more hydrochlorides are converted by one or more bases to one or more free compounds of formulae (IV), (V′) and (VI′), then said one or more free compounds are acylated in the presence of a base with one or more compounds of formula (VII) to obtain one or more mixtures of one or more compounds of formulae (VIII′), (IX′) and (X′), then said one or more compounds of formulae (VIII′), (IX′) and (X′) are reacted in the presence of an acid with one or more compounds of formula (XIV)
HO—(CR 1 R 2 ) n —CR 3 R 4 —CR 5 R 6 —OH  (XIV)

to give one or more compounds of formula (XVI)
and said one or more compounds of formula (XVI) are then cyclized in a Dieckmann reaction by the action
of a strong base to give one or more compounds of formula (XI):

where
R 1 to R 6 are independently hydrogen, methyl, ethyl or phenyl,
R 7 is optionally branched C 2 -C 8 -alkyl,
R 8 to R 12 are independently hydrogen, methyl, ethyl, fluoroalkyl having one or 2 carbon atoms and one to five fluorine atoms, halogen, methoxy, ethoxy, trifluoromethoxy or optionally methyl-, ethyl-, methoxy-, ethoxy- or halogen-substituted phenyl,
R 13 is optionally branched C 2 -C 8 -alkyl or —(CR 1 R 2 ) n —CR 3 R 4 —CR 5 R 6 —OH, and
n is 0 or 1.

2. Process according to claim 1 , where
R 1 to R 6 are independently hydrogen, methyl or ethyl,
R 7 is ethyl, n-propyl, i-propyl, n-butyl or n-hexyl,
R 8 to R 12 are independently hydrogen, methyl, ethyl, fluorine, chlorine, bromine, methoxy, ethoxy, trifluoromethoxy or optionally methyl-, ethyl-, methoxy-, ethoxy-, fluorine-, chlorine- or bromine-substituted phenyl,
R 13 is ethyl, n-propyl, i-propyl, n-butyl, n-hexyl or —(CR 1 R 2 ) n —CR 3 R 4 —CR 5 R 6 —OH, and
n is 0 or 1.

3. Process according to claim 1 , where
R 3 to R 6 are independently hydrogen or methyl,
R 7 is ethyl, n-propyl, i-propyl, n-butyl or n-hexyl,
R 8 to R 12 are independently hydrogen, methyl, ethyl, fluorine, chlorine, bromine, methoxy, ethoxy or optionally methyl-, methoxy-, fluorine- or chlorine-substituted phenyl,
R 13 is ethyl, n-propyl, i-propyl, n-butyl, n-hexyl or —(CR 1 R 2 ) n —CR 3 R 4 —CR 5 R 6 —OH, and
n is 0.

4. Process according to claim 1 , where
R 3 is hydrogen,
R 4 is hydrogen or methyl,
R 5 is hydrogen,
R 6 is hydrogen or methyl,
R 7 is ethyl, n-propyl, i-propyl, n-butyl or n-hexyl,
R 8 is hydrogen, methyl, ethyl, methoxy, ethoxy, chlorine or bromine,
R 9 is hydrogen,
R 10 is hydrogen, methyl, chlorine or bromine,
R 11 is hydrogen,
R 12 is hydrogen, methyl, ethyl, methoxy, ethoxy, chlorine or bromine,
R 13 is ethyl, n-propyl, i-propyl, n-butyl, n-hexyl or —(CR 1 R 2 ) n —CR 3 R 4 —CR 5 R 6 —OH, and
n is 0.

5. Process according to claim 1 , where
R 3 is hydrogen,
R 4 is hydrogen,
R 5 is hydrogen,
R 6 is hydrogen,
R 7 is ethyl, n-propyl or n-butyl,
R 8 is methyl, ethyl, chlorine or bromine,
R 9 is hydrogen,
R 10 is hydrogen, chlorine or bromine,
R 11 is hydrogen,
R 12 is methyl, ethyl, chlorine or bromine,
R 13 is ethyl, n-propyl, i-propyl, n-butyl, n-hexyl or —(CR 1 R 2 ) n —CR 3 R 4 —CR 5 R 6 —OH, and
n is 0.

6. Process according to claim 1 , where
R 3 is hydrogen,
R 4 is hydrogen,
R 5 is hydrogen,
R 6 is hydrogen,
R 7 is ethyl, n-propyl or n-butyl,
R 8 is methyl,
R 9 is hydrogen,
R 10 is chlorine,
R 11 is hydrogen,
R 12 is methyl,
R 13 is ethyl, n-propyl, i-propyl, n-butyl, n-hexyl or —(CR 1 R 2 ) n —CR 3 R 4 —CR 5 R 6 —OH, and
n is 0.

7. Process according to claim 1 , where
R 3 is hydrogen,
R 4 is hydrogen,
R 5 is hydrogen,
R 6 is hydrogen,
R 7 is n-propyl,
R 8 is methyl,
R 9 is hydrogen,
R 10 is chlorine,
R 11 is hydrogen,
R 12 is methyl,
R 13 is n-propyl or —CH 2 CH 2 —OH, and
n is 0.

Assignees

• Bayer Ag

Inventors

• Himmler Thomas
• Bruechner Peter
• Lindner Werner
• Hahn Julia Johanna
• Moradi Wahed Ahmed
• Fischer Reiner
• Dockner Michael

Classifications

• C07D209/54

  Spiro-condensed · CPC title

• C07C229/48 Primary

  with amino groups and carboxyl groups bound to carbon atoms of the same non-condensed ring · CPC title

• C07C233/52

  with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a ring other than a six-membered aromatic ring · CPC title

• C07C2601/14

  The ring being saturated · CPC title

• C07C2601/16

  the ring being unsaturated · CPC title