- Method for reducing residues of N-ethyl-3-phenylpropylamine in alverine
-
The invention relates to a method for reducing residues of N-ethyl-3-phenylpropylamine in alverine, and belongs to an impurity removal method of compounds. The method comprises the following steps: dissolving an intermediate alverine crude product containing impurity N-ethyl-3-phenylpropylamine into a water-insoluble organic solvent, extracting an organic layer by using an aqueous solution with appropriate pH and discarding a water layer; drying and filtering the organic layer, decompressing and evaporating the solvent to dryness. According to the method disclosed by the invention, a clear, simple and reliable solution to the residues of the N-ethyl-3-phenylpropylamine in the intermediate alverine is provided for the first time, so that the subsequently produced crude drug citric acid alverine has higher quality and the residue amount does not exceed 0.15 percent. The method has the advantages of simplicity, feasibility, low cost, few wastes and suitability for industrial popularization.
- -
-
Paragraph 0055; 0063-0068; 0085-0093
(2018/11/03)
-
- Novel citric acid alverine crystal form and preparation method thereof
-
The invention relates to a novel citric acid alverine crystal form, a preparation method thereof and a medicine composition using the crystal form as an active ingredient. The preparation method comprises the steps that phenylpropanol which is cheap and easy to obtain and serves as a start and is subjected to sulfoacid esterification and bromination to obtain 3-phenyl bromo propane; adding ethylamine hydrochloride in batches into excessive feed of the 3-phenyl bromo propane under the condition that organic base triethylamine and phase transfer catalyst exist to generate alverine free base in a 'one pot' mode; an organic layer is purified to be reacted with citric acid to produce crude citric acid alverine; the crude citric acid alverine is recrystallized through N-methyl pyrrolidone-water-DMF mixed solvent to obtain the novel crystal form B. Characteristic diffraction peaks are achieved at the positions of 4.18, 15.21, 20.53 and other positions of the value of 2 theta. The synthetic process route of the crystal form has the advantages that raw materials are easy to obtain, few reaction steps are needed, the condition is mild, operation is simple, and yield is high, and is environmentally friendly and easy to industrialize.
- -
-
Paragraph 0023; 0049-0050
(2017/03/17)
-
- A new method for the preparation of alverine citrate
-
The invention discloses a novel preparation method of alverine citrate, which comprises the following steps: reacting 3-phenylhalopropane and ethylamine hydrochloride used as initial raw materials in an alkaline system to generate diphenylpropyl ethylamine, and refining under the interaction between the organic layer and the citric acid to obtain the alverine citrate. The process route has the characteristics of accessible raw materials, fewer reaction steps, mild conditions, high yield and the like and is simple to operate, and thus, is an environment-friendly synthesis route which can easily implement industrialization.
- -
-
Paragraph 0013; 0016; 0017
(2017/01/31)
-