- Preparation method of ketorolac
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The present invention relates to the field of medicine, specifically a method of preparation of ketorolac, in the process of preparing ketorolac using alkaline hydrolyzed intermediate A5, borohydride is added, the sample of ketorolac obtained is examined in accordance with the Chinese Pharmacopoeia solution color inspection method, significantly lighter than the sample color obtained by the prior art, the preparation method of ketorolac of the present invention, compared with the prior art in the process of salting with tromethamine, compared with the method of using reducing sulfide in the process of salting with tromethamine, can avoid the risk of incandescent residue unqualified, providing convenience for the staff.
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- Preparation method of ketorolac tromethamine intermediate
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The invention belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of a ketorolac tromethamine intermediate. The preparation method comprises the following steps: reacting 5-phenyl-3,5-dioxy valeric acid with thionyl chloride to generate a compound IV; reacting the compound IV with a compound V to obtain a compound VI; and carrying out ring closing on the compound VI to obtain the ketorolac tromethamine intermediate, namely ethyl 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1,1-diformate. According to the novel method for synthesizing the ketorolac intermediate, use of dangerous chemical reagents is avoided, the synthesized intermediate does not generate new impurities, a traditional catalyst is replaced with a green catalyst, the reaction is milder, economical and environmentally friendly, the yield is high, and the method is suitable for industrial production.
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- Ketorolac tromethamine intermediate compound VI
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The invention belongs to the technical field of drug synthesis, and particularly relates to a ketorolac tromethamine intermediate compound VI. The synthesis method of the ketorolac tromethamine intermediate compound VI comprises the following steps: adding a compound V into a reaction solvent, slowly adding alkali in batches at controlled temperature, reacting at constant temperature after the addition is finished, cooling after the reaction is finished, dropwise adding a compound IV into the reaction system, performing temperature-controlled reaction after dropwise adding is completed, and adjusting pH after the reaction is completed; evaporating under reduced pressure to remove the solvent, adding an extraction solvent into residues for extraction, collecting an organic layer, filtering and drying to obtain the compound VI. The invention provides a novel method for synthesizing a ketorolac tromethamine intermediate compound by using the intermediate, and the method is simple and convenient to operate; starting raw materials are easy to obtain, highly toxic and highly corrosive substances are not used in the reaction, the reaction steps are few, the operation is simple, and the method is suitable for industrial production; the reaction speed is high, impurities are few, the reaction yield and purity are improved, and the cost is reduced.
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- Ketorolac tromethamine intermediate compound
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The invention belongs to the technical field of medicine synthesis, and particularly relates to a ketorolac tromethamine intermediate compound IV. A synthesis method of the ketorolac tromethamine intermediate compound IV comprises the following steps: adding a compound II into an organic solvent, dropwise adding thionyl chloride at a controlled temperature, reacting at a constant temperature after dropwise adding, performing TLC detection, filtering after the reaction is finished, concentrating and drying to obtain the compound IV. The invention provides the novel ketorolac tromethamine intermediate compound IV and a novel method for synthesizing the ketorolac tromethamine intermediate compound by using the ketorolac tromethamine intermediate compound, and the novel intermediate is simple and convenient to operate in the ketorolac tromethamine synthesis process; the novel method avoids use of highly toxic and highly corrosive substances, has few reaction steps, is simple to operate, and is suitable for industrial production; the reaction yield and purity are improved, and the cost is reduced.
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- Improved preparation method of ketorolac intermediate
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The invention discloses an improved preparation method of a ketorolac intermediate. The intermediate is (5-Benzoyl-1H-pyrrol-2-yl)methanetricarboxylic acid triethyl ester (M-1). The method comprises the following steps: subjecting 2-benzoylpyrrole, methane tricarboxylic acid triethyl ester, manganese acetate dihydrate (trivalent), sodium acetate and acetic anhydride to reacting in an organic solvent; adding an aqueous sodium hydrogen sulfite solution for extraction and liquid separation; and conducting vacuum concentration on an organic phase and pulping the an organic phase with an alcohol solvent. According to the method, post-treatment problems caused by the existence of a large amount of manganese ion compounds and a large amount of solvent acetic acid are effectively solved; meanwhile, the problems of high energy consumption, long period, high cost and the like caused by later concentration are reduced; and the obtained intermediate has the advantages of high purity, high yield and the like and is suitable for industrial production.
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Paragraph 0041-0052
(2021/07/01)
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- Synthesis process of ketorolac
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The invention discloses a synthesis process of ketorolac, and relates to the technical field of medicine synthesis. The synthesis process solves the technical problems that the existing process can generate a large amount of liquid and solid wastes, and the environment protection is not facilitated. Hydrogen peroxide with side products being water is used as an oxidizing agent; malysite is used asa catalyst; a large number of manganese salts are replaced; when 1kg of ketorolac is reduced, 3.5 to 6.1kg of discharged liquid and solid wastes are reduced; the green and environment-friendly effects are achieved. Benzoyl chloride is directly used as raw materials; the one-step reaction is reduced; the synthesis process is simpler; the methyl tertiary butyl ether is used for replacing the flammable and combustible diethyl ether; the process production safety is improved. The synthesis process has the advantages that the operation is easy; the process conditions can be easily controlled; thefinal product purification and aftertreatment are simple.
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Paragraph 0021-0037
(2018/07/30)
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- Solvent free oxidative radical substitution process. Synthesis of pyrrole fused systems
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A xanthate-based, solvent free, homolytic substitution on selected substituted pyrrole systems is described. Additionally, a practical entry for the rapid construction of pyrrole fused systems using this solventless radical addition followed by a double nucleophilic alkylation sequence, is also reported.
- Flórez-López, Edwin,Gomez-Pérez, Liliana B.,Miranda, Luis D.
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supporting information; experimental part
p. 6000 - 6002
(2010/11/21)
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- Process for preparing pyrrolizine derivatives
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This invention relates to novel processes for preparing substituted pyrrolizine compounds. More particularly, it relates to novel processes for preparing 5-aroyl-2,3-dihydro-1H-pyrrolizine-1,1-dicarboxylate of the following formula (I) from pyrrole. STR1
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- Process for preparing 5-aroyl-2,3-dihydro-1H-pyrrolizine-1,1-dicarboxylates (I) and intermediates therefor
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5-Aroyl-2,3-dihydro-1H-pyrrolizine-1,1-dicarboxylates of the formula STR1 are prepared from 2-aroylpyrroles. Hydrolysis and mono-decarboxylation of these compounds affords ketorolac and related compounds.
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- Process for preparing 5-aroyl-2,3-dihydro-1H-pyrrolizine-1,1-dicarboxylates (II) and intermediates therefor
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5-Aroyl-2,3-dihydro-1H-pyrrolizine-1,1-dicarboxylates of the formula STR1 are prepared from 2-aroylpyrroles. Hydrolysis and mono-decarboxylation of these compounds affords ketorolac and related compounds.
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