39746-01-5Relevant articles and documents
Preparation method of carboprost tromethamine intermediate
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Paragraph 0076-0079, (2021/06/22)
The invention provides a preparation method of a carboprost tromethamine intermediate. The method comprises the following steps: A) carrying out an oxidation reaction on benzoyl corey lactone alcohol shown in a formula I under the action of a catalyst and an oxidizing agent to obtain benzoyl corey lactone aldehyde shown in a formula II; B) reacting the benzoyl corey lactone aldehyde as shown in the formula II with dimethyl (2-oxoheptyl) phosphonate under the action of alkali to obtain a 15-ketone crude product as shown in a formula III, and recrystallizing the 15-ketone crude product to obtain a 15-ketone pure product; and C) carrying out methylation reaction on the 15-ketone pure product to obtain the carboprost tromethamine intermediate as shown in a formula IV. According to the invention, the use of reagents with high toxicity and serious environmental pollution is avoided; when the carboprost intermediate 15-ketone is prepared, a mixed solvent is adopted for recrystallization, so that column chromatography is omitted, operation is easy and convenient, reagents are saved, and cost is reduced; and in the methylate preparation process, ultralow temperature is avoided, and the reaction time is shortened, so that the energy consumption is reduced, and the purity and the yield are relatively high.
Carboprost tromethamine related impurity L-amyl 15-ketone and preparation method thereof
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Paragraph 0025-0026; 0048-0053, (2021/01/04)
The invention relates to a carboprost tromethamine related impurity L-amyl 15-ketone and a preparation method thereof. The preparation method comprises the following steps of: (1) in the presence of afifth organic solvent, carrying out dehydrogenation reaction on methyl triphenyl phosphine halide by using strong base, adding ethyl valerate after reaction for a certain time, continuously reactingfor a certain time to obtain 1-triphenylphosphine 2-hexanone; and (2) carrying out wittig reaction on the 1-triphenylphosphine 2-hexanone obtained in the step (1) and a second organic solvent solutionof benzoyl corey lactone aldehyde to obtain a pentyl-15 ketone crude product. The method has the advantages of simple and convenient operation, high safety, and high yield and purity of an obtained product under optimal conditions, and can meet the requirements for impurity research.
15-ketone preparation method
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Paragraph 0014, (2016/10/10)
The present invention relates to a drug intermediate 15-ketone preparation method in chemical field. The preparation method comprises the following steps: (1) (-)-Corey lactone benzoate, an oxidizing agent and a catalyst are added into a first organic solvent for oxidation to obtain a reaction solution A; (2) after a dilute acid is dropwise added into the reaction solution A obtained in the step (1), the solution is stirred and filtered, the filtrate is extracted directly with the first organic solvent, an organic phase is washed with water, dehydrated with a desiccant and filtered to obtain a (-)-Corey lactone benzoate aldehyde solution; (3) Wittig reagent is added into the (-)-Corey lactone benzoate aldehyde solution obtained in the step (2) for Wittig reaction to obtain a reaction solution B, the reaction solution B is concentrated, a second organic solvent is added, and after cooling and crystallization, a crystallization liquid is obtained; and (4) the crystallization liquid obtained in the step (3) is filtered, the filter cake is washed with a third organic solvent, the filter cake is dissolved by the first organic solvent for impurity removal, and after filteration and concentration, an oil matter is obtained. The drug intermediate 15-ketone preparation method has the advantages of good product quality and the like.