The prep work approach of NAftifine Hydrochloride Cream provided by the invention makes up the following steps that are performed in order:
( 1) N-methyl-1-naphthylmethylamine hydrochloride as resources and also the organic ether solvent as response solvent are mixed in proportion;
(2) in above-mentioned mixed solution, add alkali metal carbonate and catalyst PEG-600, react 1-4h under the temperature of 30 ℃-100 ℃, by N-methyl-1-naphthylmethylamine hydrochloride Free as N-methyl-1-naphthylmethylamine;
(3) in above-mentioned reaction solution, drip cinnamyl chloride, the time for adding is 1-10h, carry out condensation reaction, then continue to react 4-10h to react completely, make naftifine solution;
( 4) prior naftifine solution is filtered, then in the filtrate, drip the ethyl acetate saturated service of hydrogen chloride to acquire naftifine hydrochloride unrefined item;
( 5) prior naftifine hydrochloride crude item adopts ethyl acetate as well as methanol mixed solvent to perform recrystallization and can make explained naftifine hydrochloride.
The organic ether solvent in the explained action (1) is ether, methyl tert-butyl ether, methyl isobutyl ether, isopropyl ether, anisole, tributyl methyl ether, tetrahydrofuran, dioxane.
In the explained step (2 ), the alkali steel carbonate is among sodium carbonate as well as potassium carbonate, and also the usage is 1.5-3 matchings of N-methyl-1-naphthylmethylamine hydrochloride.
In the defined action (2 ), the intake of PEG-600 is 0.05-0.5 matching of N-methyl-1-naphthylmethylamine hydrochloride.
In the defined action (3 ), the usage of cinnamyl chloride is 1.0-2.0 matching of N-methyl-1-naphthylmethylamine hydrochloride.
In the defined step (4 ), the usage of hydrogen chloride in the saturated ethyl acetate solution is 1-1.5 matchings of N-methyl-1-naphthylmethylamine hydrochloride.
In the described action (5 ), the quantity ratio of ethyl acetate and also methanol is 1: 0.5-2.0.
Above-mentioned reaction steps are as complies with:
The prep work technique of naftifine hydrochloride supplied by the invention has the adhering to advantages:
1. The raw material N-methyl-1-naphthylmethylamine hydrochloride is not purified by free, but reacts with alkali metal carbonate under the action of a catalyst, which is freed by alkalization, and directly participates in further condensation reaction, which simplifies the operation process;
2. The organic ether solvent replaces the toluene, acetonitrile, etc. reported in the literature as the reaction solvent. The test results show that the reaction is complete, the impurities are less, and the generated impurities are easily removed in the post-processing process, thus helping to obtain high-quality products ;
3. after the reaction finishes, the post-processing operation process is simple, and the organic solvent saturated solution of hydrogen chloride is directly added dropwise after the filtration to obtain the naftifine hydrochloride crude product with high yield and better quality;
4. Cleanse naftifine hydrochloride crude product by recrystallization technique to get naftifine hydrochloride item with high return as well as excellent quality, the recrystallization return can get to more than 80%, and the item material can reach more than 98% (HPLC normalized Law);.
5. The prep work approach has the advantages of easy operation procedure, high return, inexpensive, and also very easy industrialization.