Method for producing enaminocarbonyl compounds
View Patent ↗The present invention relates to a process for preparing enaminocarbonyl compounds by reacting compounds of the formula (II) with compounds of the formula (III) in which the A, R 1 , R 2 and Z radicals are each as defined in the description, in the presence of a Brønsted acid.
1. A process for preparing a compound of formula (I)
comprising reacting a compound of formula (II)
with an amine of formula (III)
in the presence of a Brønsted acid, where
R 1 is hydrogen, alkyl, or haloalkyl;
R 2 is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, halocycloalkyl, alkyloxyalkyl, halocycloalkylalkyl, aryl or arylalkyl;
Z is selected from the chemical moieties —(C═O)OR 3 and —(C═O)NR 1 CH 2 A, in which R 3 is selected from C 1-12 -alkyl, C 3-8 -cycloalkyl, C 2-12 -alkenyl, C 2-12 -alkynyl, C 6-8 -aryl, C 7-19 -arylalkyl or C 7-19 -alkylaryl, each of which may be substituted by one or more radicals selected from —R′, —OR′, —SR′, —NR′ 2 , —SiR′ 3 , —COOR′, —(C═O)R′, —CN and —CONR 2 ′, where R′ is hydrogen or C 1-12 -alkyl;
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.
2. The process according to claim 1 , wherein the Brønsted acid is selected from the group consisting of H 3 PO 4 , H 2 SO 4 , HCl, HBr, HF, KHSO 4 , trifluoroacetic acid, acetic acid, methanesulphonic acid and p-toluenesulphonic acid.
3. The process according to claim 1 , where
R 1 is hydrogen, C 1-12 -alkyl, or C 1-12 -haloalkyl;
R 2 is C 1-12 -alkyl, C 1-12 -haloalkyl, C 2-12 -alkenyl, C 2-12 -haloalkenyl, C 2-12 -alkynyl, C 3-8 -cycloalkyl, C 3-8 -cycloalkylC 1-12 -alkyl, C 3-8 -halocycloalkyl, C 1-12 -alkoxy, C 1-12 -alkyloxyalkyl, C 3-8 -halocycloalkylC 1-12 -alkyl or C 6-14 -ArylC 1-12 -alkyl;
Z is selected from the chemical moieties —(C═O)OR 3 and —(C═O)NR 1 CH 2 A, in which R 3 is selected from C 1-12 -alkyl, C 3-8 -cycloalkyl, C 2-12 -alkenyl, C 2-12 -alkynyl, C 6-8 -aryl, C 7-19 -arylalkyl or C 7-19 -alkylaryl, each of which may be substituted by one or more radicals selected from —R′, —OR′, —SR′, —NR′ 2 , —SiR′ 3 , —COOR′, —(C═O)R′, —CN and —CONR 2 ′, where R′ is hydrogen or C 1-12 -alkyl;
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.
4. The process according to claim 1 , where
A is 6-fluoropyrid-3-yl, 6-chloropyrid-3-yl, 6-bromopyrid-3-yl, 5 fluoro-6-chloropyrid-3-yl, 5,6-dichloropyrid-3-yl, 5-bromo-6-chloropyrid-3-yl, 5-fluoro-6-bromopyrid-3-yl, 5-chloro-6-bromopyrid-3-yl, 5,6-dibromopyrid-3-yl, 5-methyl-6-chloropyrid-3-yl, 5-chloro-6-iodopyrid-3-yl or 5-difluoromethyl-6-chloropyrid-3-yl;
R 1 is methyl, ethyl, n-propyl, isopropyl, 2-fluoroethyl, or 2,2-difluoroethyl;
Z is a chemical moiety —(C═O)OR 3 in which R 3 is methyl, ethyl, n-propyl, isopropyl or butyl; and
R 2 is C 1 -C 12 -alkyl.
5. The process according to claim 1 , where
A is 6-chloropyrid-3-yl, 6-bromopyrid-3-yl, 5-fluoro-6-chloropyrid-3-yl or 5-fluoro-6-bromopyrid-3-yl;
R 1 is methyl, ethyl, n-propyl, isopropyl, 2 fluoroethyl or 2,2-difluoroethyl;
Z is —CO 2 CH 2 CH 3 or —CO 2 CH 3 ; and
R 2 is ethyl, isopropyl or butyl.
6. The process according to claim 1 , wherein the reacting is performed in a solvent which is at least one selected from the group consisting of dioxane, butyronitrile, propionitrile, acetonitrile, DME, toluene, methyl-THF, dichlorobenzene, chlorobenzene, n-heptane, isobutanol, n-butanol, ethanol, methyl tert-butyl ether, and isopropyl ethyl ether.
7. The process according to claim 1 , wherein the reacting is performed at a temperature from 20° C. to 150° C.
8. The process according to claim 1 , wherein the molar ratio of the compound of the formula (II) to the compound of the formula (III) is 1 to 6.
9. The process according to claim 1 , wherein compound (I) is 4-[[(6-chloropyridin-3-yl)methyl](2,2-difluoroethyl)amino]furan-2(5H)-one.