Method for preparing intermediate of uracil compound containing isoxazoline
A method for preparing an intermediate of a uracil compound containing isooxazoline includes the steps of: making 3-amino-4,4,4-trifluorocrotonic acid methyl ester react with substituted aryl carbamate; in a reaction process, continuously evaporating water and byproduct alcohol in the system; and conducting processing to obtain the intermediate of the uracil compound containing isooxazoline. Using this method the selectivity of the reaction and the utilization rate of raw materials are improved; the hydrolysis products, impurities and tar are reduced; the reaction time is greatly shortened; and the productivity is improved. After one recrystallization of crude products, an intermediate product with purity of more than 97% can be obtained, and quantitative yield can be more than 85%.
1 . A method for preparing an intermediate of a uracil compound containing isooxazoline, comprising:
reacting a compound of formula III with a compound of formula IV in the presence of a catalyst; and
continuously removing water and alcohol generated in the reaction by evaporation to obtain the intermediate of the uracil compound containing isooxazoline of formula II:
wherein:
R 1 and R 2 are the same or different, and are independently selected from hydrogen, fluorine, and chlorine;
R 3 is hydrogen or C 1 -C 4 alkyl;
R 4 is hydrogen, CO 2 R 7 , or CH 2 OR 8 ;
R 5 is hydrogen, CO 2 R 7 , or CH 2 OR 8 ;
R 6 is hydrogen, C 1 -C 4 alkyl, or C 1 -C 4 haloalkyl;
R 7 is C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, allyl, or propargyl;
R 8 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkyl carbonyl;
R 9 is C 1 -C 4 alkyl;
R 10 is C 1 -C 4 alkyl, and
the catalyst is 1,8-diazabicyclo[5.4.0]undec-7-ene or a salt thereof.
2 . The method for preparing the intermediate of the uracil compound containing isooxazoline according to claim 1 , wherein:
R 1 and R 2 are the same or different, and are independently selected from hydrogen, fluorine, and chlorine;
R 3 is hydrogen or C 1 -C 4 alkyl;
R 4 is hydrogen;
R 5 is CO 2 R 7 ;
R 6 is C 1 -C 4 haloalkyl;
R 7 is selected from methyl, ethyl, n-propyl, n-butyl, isopropyl, isobutyl, tert-butyl, trifluoroethyl, allyl, and propargyl;
R 9 is methyl or ethyl; and
R 10 is methyl or ethyl.
3 . The method for preparing the intermediate of the uracil compound containing isooxazoline according to claim 1 , wherein the reaction is carried out in the presence of an alkali, and a molar ratio of the alkali to the compound of formula III is 0.5:1-3:1.
4 . The method for preparing the intermediate of the uracil compound containing isooxazoline according to claim 1 , wherein an amount of the catalyst is 0.001%-10% of a weight of the compound of formula III.
5 . The method for preparing the intermediate of the uracil compound containing isooxazoline according to claim 4 , wherein the amount of the catalyst is 0.1%- 5% of the weight of the compound of formula III.
6 . The method for preparing the intermediate of the uracil compound containing isooxazoline according to claim 3 , wherein the alkali is one or two selected from the group consisting of potassium carbonate, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, and cesium bicarbonate.
7 . The method for preparing the intermediate of the uracil compound containing isooxazoline according to claim 6 , wherein the alkali is one or two selected from the group consisting of potassium carbonate, sodium carbonate, potassium bicarbonate and sodium bicarbonate, wherein a molar ratio of the alkali to the compound of formula III is 0.5:1-2:1.
8 . The method for preparing the intermediate of the uracil compound containing isooxazoline according to claim 1 , wherein the reaction is carried out in the presence of a water carrying agent or a mixed solvent that is 2-20 times a weight of the compound of formula III, and the mixed solvent comprises the water carrying agent and a polar aprotic solvent, wherein a weight of the polar aprotic solvent is 20%- 70% of the weight of the mixed solvent.
9 . The method for preparing the intermediate of the uracil compound containing isooxazoline according to claim 8 , wherein the reaction is carried out in the presence of a water carrying agent selected from the group consisting of n-propyl acetate, isopropyl acetate, n-butyl acetate, methyl isopropyl ketone, methyl isobutyl ketone, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, 2-methyl tetrahydrofuran, and acetonitrile; and the mixed solvent comprises a compound selected from the group consisting of toluene, chlorobenzene, n-propyl acetate, isopropyl acetate, methyl isopropyl ketone, methyl isobutyl ketone, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, 2-methyltetrahydrofuran, and acetonitrile; and the polar aprotic solvent in the mixed solvent is N,N-dimethylformamide, dimethyl sulfoxide, or N-methylpyrrolidone.
10 . A method for production of a compound of formula I, comprising: producing a compound of formula II using a method according to claim 1 , and converting the compound of formula II to obtain the compound of formula I,
11 . The method for preparing the intermediate of the uracil compound containing isooxazoline according to claim 8 , wherein the mixed solvent comprises a compound selected from the group consisting of toluene, chlorobenzene, n-propyl acetate, isopropyl acetate, methyl isopropyl ketone, methyl isobutyl ketone, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, 2-methyltetrahydrofuran, and acetonitrile; and the polar aprotic solvent in the mixed solvent is N,N-dimethylformamide, dimethyl sulfoxide, or N-methylpyrrolidone.