Method for preparing 4-aminobut-2-enolides
View Patent ↗Process for preparing 2,2-difluoroethylamine derivatives, wherein compounds of the general formula (IV) are reduced to the corresponding 2,2-difluoroethylamine derivatives of the general formula (III), where the A radical is as defined in the description:
1. A process for preparing a 4-aminobut-2-enolide compound of formula (I)
comprising reacting a compound of formula (II)
with an amine of formula (III)
where
R 1 is hydrogen, alkyl, fluoroalkyl, alkenyl, fluoroalkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, fluorocycloalkyl, alkoxy, alkoxyalkyl, fluorocycloalkylalkyl or arylalkyl;
R 2 is alkyl, aryl or arylalkyl;
Z is hydrogen, an alkali metal or an alkaline earth metal;
A is pyrid-2-yl or pyrid-4-yl, or is pyrid-3-yl which is optionally 6-substituted by fluorine, chlorine, bromine, methyl, trifluoromethyl or trifluoromethoxy, or is
in which
X is halogen, alkyl or fluoroalkyl, and
Y is halogen, alkyl, fluoroalkyl, or fluoroalkoxy.
2. The process according to claim 1 , wherein the compound of the formula (II) is obtained by reacting a compound of formula (V)
wherein
R 3 alkyl, with the exception of ethyl, or cycloalkyl; and
R 4 is alkyl, cycloalkyl, fluoroalkyl, aryl or arylalkyl with a base.
3. The process according to claim 2 , wherein the compound of formula (II) is obtained by the following scheme proceeding from a compound of formula (V) by reaction with sodium alkoxide:
where
R 2 is alkyl, aryl or arylalkyl;
R 3 is alkyl, with the exception of ethyl, or cycloalkyl; and
R 4 is alkyl, cycloalkyl, fluoroalkyl, aryl or arylalkyl.
4. The process according to claim 2 , wherein the compound of formula (II) is obtained by the following scheme proceeding from a compound of formula (V) by reaction with potassium tert-butoxide:
where
R 3 is alkyl, with the exception of ethyl, or cycloalkyl; and
R 4 is alkyl, cycloalkyl, fluoroalkyl, aryl or arylalkyl.
5. The process according to claim 1 , wherein the compound of formula (II) is obtained by the following scheme proceeding from malonic esters and chloroacetyl chloride:
where R 2 is alkyl, aryl or arylalkyl.
6. A process for preparing a compound of formula (V)
comprising reacting a compound of formula (IV)
with an alkyl chloro acetate of formula (VI)
where
R 3 is alkyl, with the exception of ethyl, or cycloalkyl;
R 4 is alkyl, cycloalkyl, fluoroalkyl, aryl or arylalkyl.
7. The process according to claim 1 , wherein A is
in which
X is halogen, alkyl or fluoroalkyl, and
Y is halogen, alkyl, fluoroalkyl, or fluoroalkoxy.
8. The process according to claim 7 , wherein A is
in which
X is halogen, alkyl or fluoroalkyl and
Y is halogen, alkyl, fluoroalkyl, fluoroalkoxy, azido or cyano.
9. The process according to claim 1 , wherein
R 1 is hydrogen, alkyl, fluoroalkyl, alkenyl, fluoroalkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, fluorocycloalkyl, fluorocycloalkylalkyl, or alkoxyalkyl,
R 2 is C 1 -C 12 -alkyl, C 6 -aryl, or aralkyl, and
Z is an alkali metal or hydrogen.
10. The process according to claim 1 , wherein
R 1 is methyl, ethyl, propyl, vinyl, allyl, propargyl, cyclopropyl, alkoxyalkyl, 2 fluoroethyl, 2,2-difluoroethyl, or 2-fluorocyclopropyl, and
R 2 is C 1 -C 12 -alkyl, and
Z is hydrogen, sodium, or potassium.
11. The process according to claim 1 , wherein
R 1 is methyl, ethyl, n-propyl, n-prop-2-enyl, n-prop-2-ynyl, cyclopropyl, methoxyethyl, 2-fluoroethyl, or 2,2-difluoroethyl, and
R 2 is methyl or ethyl, and
Z is sodium or hydrogen.
12. The process according to claim 1 , wherein
A is pyrid-2-yl, which is optionally 6-substituted by fluorine, chlorine, bromine, methyl, trifluoromethyl, or trifluoromethoxy.
13. The process according to claim 1 , wherein
A is pyrid-3-yl, which is optionally 6-substituted by fluorine, chlorine, bromine, methyl, trifluoromethyl, or trifluoromethoxy.
14. The process according to claim 1 , wherein
A is pyrid-4-yl, which is optionally 6-substituted by fluorine, chlorine, bromine, methyl, trifluoromethyl, or trifluoromethoxy.
15. The process according to claim 2 , wherein the base is alkoxide.
16. The process according to claim 6 , wherein the alkyl chloroacetate is ethyl chloroacetate.