51 results about "Propanoyl chloride" patented technology

The invention relates to a preparation method of an agomelatine intermediate, which belongs to the field of drug intermediates, and comprises the following four steps: acylating chlorination and amidation of 7-methoxy-1-naphthyl propionic acid, Hofmann degradation of 7-methoxynaphthalene-1-yl propanamide, and post-treatment. 7-methoxy-1-naphthyl propionyl chloride obtained by carrying out acylating chlorination on the 7-methoxy-1-naphthyl propionic acid is subjected to amidation to obtain 7-methoxy-1-naphthyl propionamide, and then the 7-methoxy-1-naphthyl propionamide is subjected to Hofmann degradation to obtain the agomelatine intermediate 7-methoxy-1-naphthyl ethylamine. The preparation method disclosed by the invention is short in reaction step and mild in reaction condition, the reaction temperature is-5 to 100 DEG C, and the reaction pressure is normal pressure; an azide is not used, Raney nickel catalysis or palladium carbon catalytic hydrogenation operation is not involved, and the reaction operation is simple and safe; the total yield of the 7-methoxy-1-naphthyl ethylamine can reach 67.1%-78.4%, and the liquid phase purity can reach 98.1%-98.9%.

The invention is applicable to the technical field of organic intermediate preparation processes, and provides a method for preparing D-(+)-2-chloropropionyl chloride by adopting a microchannel continuous flow reactor, wherein the method comprises the steps: dissolving L-lactic acid and a catalyst 2,6-di-tert-butylpyridine in dichloromethane to obtain a homogeneous solution A; dissolving thionyl chloride in dichloromethane to obtain a homogeneous solution B; respectively and simultaneously pumping the homogeneous solution A and the homogeneous solution B into a micro-mixer in a micro-channel continuous flow reaction device; introducing a mixed solution of the micro-mixer in the micro-channel continuous flow reaction device into a micro-reactor; and collecting the effluent of the micro-reactor, recycling a solvent by normal pressure distillation, and carrying out reduced pressure distillation to obtain the D-(+)-2-chloropropionyl chloride with optical purity. The micro-channel continuous flow reactor used in the method is in full-automatic formation production, the control precision is high, the reaction process is safe and controllable, and the obtained D-(+)-2-chloropropionyl chloride is high in yield and high in optical purity; and the mass and heat transfer performance is good, the D-(+)-2-chloropropionyl chloride can be continuously prepared on a large scale, and the application prospect is wide.

The invention discloses a multi-carboxyl chelating agent as well as a preparation method and application thereof. The preparation method comprises the following steps: (1) adding dipentaerythritol andpropionyl chloride into a three-neck flask to obtain a viscous liquid intermediate I; (2) adding the viscous liquid intermediate I obtained in the step (1) into a four-neck flask, then adding a firstsolvent dimethyl sulfoxide into the four-neck flask, and then adding sodium chloroacetate into a solution containing solvents such as dimethyl sulfoxide to obtain a solid product intermediate II; and(3) adding the solid product intermediate II in the step (2) into a second solvent dimethylformamide, and adding hexamethylene diisocyanate (HDI) under magnetic stirring to obtain the multi-carboxylchelating agent. According to the preparation method of the multi-carboxyl chelating agent, the heavy metal chelating agent with dual functions of flocculation and chelating is successfully prepared.

The invention relates to the technical field of medicine preparation, and discloses a preparation method of rotigotine, which uses 5-methoxy-2-tetralone as an initial raw material, reacts with R-α-methylbenzylamine, and undergoes desorption Benzyl reduction, chiral resolution of S-mandelic acid, and then react with propionyl chloride reagent to generate amide compound, then reduce it with sodium borohydride reagent, and finally react with 2-(thiophen-2-yl) 2-nitrobenzenesulfonic acid ethyl Ester reaction to give rotigotine. The preparation process route is that the rotigotine of the present invention has mild preparation conditions, simple operation, high yield of key intermediates, high optical purity, easy industrial scale-up production, and good application prospects.

A preparation method of 3,3,3-trifluoropropionic acid. The preparation method of the present invention first uses 2-chloro-1-1-difluoroethylene (a) as a raw material to perform carbonyl insertion reaction with carbon monoxide to obtain 3,3-difluoro 2-acryloyl chloride (b); then use HF to treat 3 ,3‑Difluoro 2‑acryloyl chloride is subjected to fluorination reaction to obtain 3,3,3‑trifluoropropionyl fluoride (c), and finally 3,3,3‑trifluoropropionyl fluoride is hydrolyzed to obtain trifluoropropionyl fluoride Acid (d). The preparation method of the invention has cheap and easy-to-obtain raw materials, mild conditions, high conversion rate of starting materials, and the total yield of the three-step reaction can reach more than 50%.

The invention discloses a method for continuously preparing voriconazole intermediate 2-fluoro-3-oxyvaleric acid ethyl ester, comprising: feeding a reaction solvent, 2-fluoro-ethyl acetate, propionyl chloride and sodium hydrogen into a reaction kettle for reaction, Then add boric acid and acid anhydride, then send the reaction solution into the centrifuge, the supernatant is continuously sent to the middle of the rectification tower for heating and rectification, the light components are condensed at the top of the tower, and refluxed into the reaction kettle, and the heavy component products are extracted from the tower Bottom collection, that is. The invention realizes the continuous production process of the reaction of 2-fluoro-ethyl acetate and propionyl chloride and the separation of 2-fluoro-3-oxopentanoic acid ethyl ester through the reaction kettle coupling rectification tower. By adding boric acid and anhydride after the reaction, the reaction by-product 2-fluoro-3-oxopentanoic acid is converted into 2-fluoro-3-oxovaleric acid- which is easily separated from the main product O 3, O 4‑boryl diacetate improves the purity of the product, realizes low energy consumption, simple and rapid continuous production, the product yield is greater than 90%, and the purity is above 98%.

The invention discloses a preparation method of pramipexole hydrochloride, which comprises the following steps: p-aminocyclohexanol is condensed and protected by propionyl chloride to obtain p-propionyl cyclohexanol, and then catalyzed to obtain p-propionyl cyclohexanone, and then Oxidative bromination and Hantzsch condensation to give 2-amino-6-propionylamino-4,5,6,7-tetrahydrobenzothiazole, and reduction with diisobutylaluminum hydride to give 2-amino-6-propylamino ‑4, 5, 6, 7‑tetrahydrobenzothiazole, finally separated by L‑(+)‑tartaric acid and salified to obtain pramipexole hydrochloride. The preparation method of pramipexole hydrochloride proposed by the invention has cheap and easy-to-obtain raw materials, convenient and simple operation, novel route, environmental protection, high yield, and the prepared pramipexole hydrochloride has good purity.

The invention discloses a detection method for the purity of 2-chloropropionyl chloride, which utilizes the property that the acid chloride is easy to react with alcohols to form esters for derivatization treatment, avoiding the corrosion caused by the direct measurement of 2-chloropropionyl chloride and the inaccurate measurement results. Stable, then by gas chromatographic detection, the final area normalization method calculates 2-chloropropionyl chloride purity. The detection method can effectively separate the main component peak and the impurity peak of 2-chloropropionyl chloride, which greatly improves the detection sensitivity of 2-chloropropionyl chloride, so that the purity of 2-chloropropionyl chloride can be detected simply, quickly and stably. The detection method is simple in operation, high in accuracy, high in sensitivity and precision, good in stability and good in reproducibility.

The invention relates to an Alectinib intermediate and a preparation method of Alectinib. The method comprises the following steps of: carrying out condensation on 2-nitro-4-cyanophenyl acetate with 2-methyl-2-(4-ethyl-3-substituted)phenyl propionate / propionyl chloride, hydrolyzing ester groups, carrying out amination by dimethylamine hydrochloride, then carrying out a reduction-cyclization reaction to obtain an intermediate 2,3,6-trisubstituted indole derivative, and carrying out a cyclization reaction with a cyclization reagent to prepare Alectinib. The method has the advantages of cheap andeasily-obtained raw materials, short process flow and safe and simple operation; the related unit reactions have high unit reaction selectivity and small waste water amount; and green and simple production of the Alectinib is facilitated.

The present invention discloses a process for the preparation of Iopamidol of formula (II) and comprising the following steps: a) reacting the Compound (I) wherein X is OR2 or R3, and wherein R2 and R3 are a Ci-C6 linear or branched alkyl, C3-C6 cycloalkyl, C6 aryl, optionally substituted with a group selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, t-butyl and phenyl, with the acylating agent (S)-2-(acetyloxy)propanoyl chloride in a reaction medium to provide the acetyloxy derivative of Compound (I); b) hydrolyzing the intermediate from step a) with an aqueous solution at a pH comprised from 0 to 7, by adding water or a diluted alkaline solution such as sodium hydroxide or potassium hydroxide, freeing the hydroxyls from the boron-containing protective groups, obtaining the N—(S)-2-(acetyloxy)propanoyl derivative of Compound (II); c) alkaline hydrolysis to restore the (S)-2-(hydroxy)propanoyl group and to obtain Iopamidol (II) and optional recovery of the boron derivative from the solution obtained in step b). The boron-containing protective group is versatile, efficient and recyclable. A one-pot synthesis, without intermediate isolation is provided, leading to a decreasing of recovered and recycled solvents and a significant increasing in the yield, representing a significant advantage in terms of cost-effectiveness of the entire process and environmental awareness.

A process for the preparation of (S)-N,N′-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-[(2-hydroxy-1-oxo-propyl)amino]-2,4,6-triiodo-1,3-benzendicarboxamide (iopamidol) starting from 5-amino-N,N′-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-2,4,6-triiodo-1,3-benzenedicarboxamide (II) which process comprises a) reacting the compound of formula (II) with a suitable protecting agent, to give a compound of formula (III) wherein R is a group of formula A or B wherein R1 is a hydrogen atom, a C1÷C4 straight or branched alkoxy group, R2 is hydrogen, a C1÷C4 straight or branched alkoxy group and R3 ?is a C1÷C4 straight or branched alkyl group, a trifuoromethyl or a trichloromethyl group; b) acylating the amino group in position 5 of the intermediate compound of formula (III), by reaction with a (S)-2-(acetyloxy)propanoyl chloride to give a compound of formula (IV) wherein R is as defined above; and c) removing all the acyl groups present in the compound of formula (IV) under basic conditions, with prior cleavage of the cyclic protections of the hydroxy groups in the carboxamido substituents under acidic conditions, when R is a group of formula A carboxamido hydroxy groups under acidic conditions. The invention also refers to the new intermediates of formula (III) and (IV) wherein —R is a group A.