166 results about "Chloroformic acid" patented technology

The invention concretely relates to R-amisulpride medicine salt, a preparation method, a crystal form and application thereof in preparing a medicine for treating diabetes. The preparation method comprises the following steps: by adopting 2-aminomethyl-N-ethyl pyrrolidine as a raw material, and adopting L-tartaric acid, for splitting to obtain (R)-2-aminomethyl-N-ethyl pyrrolidine; directly condensing amisulpride acid and the (R)-2-aminomethyl-N-ethyl pyrrolidine under the catalysis of isopropyl chlorocarbonate and triethylamine, thus obtaining R-amisulpride; reacting the R-amisulpride obtained in the step (2) and acid to obtain the R-amisulpride medicine salt. The preparation method has the advantages of simplicity in operation, high safety, good product quality, low cost and the like, and is convenient for scale production.

The invention discloses a method for preparing sodium, 8-(2-hydroxybenzamido)octanoate which is a drug intermediate. The method comprises the following steps of reacting salicylamide, which serves as a raw material, with ethyl chloroformate to produce an intermediate 2H-benzo[e][1,3]oxazine-2,4(3H)-dione, reacting the intermediate with 8-bromooctanoic acid ethyl ester, carrying out hydrolysis so as to obtain 8-(2-hydroxybenzamido)octanoic acid, and then, reacting 8-(2-hydroxybenzamido)octanoic acid with sodium hydroxide so as to obtain the final product, namely sodium, 8-(2-hydroxybenzamido)octanoate. According to the method, the raw material reacts with ethyl chloroformate to produce the intermediate 2H-benzo[e][1,3]oxazin-2,4(3H)-dione, so that the yield of the reaction is greatly increased, the selectivity of reaction is greatly improved, the production cost is reduced, the production of byproducts is lowered, industrial production is facilitated; and the method is environment-friendly.

The invention relates to the field of chemical synthesis and particularly relates to a preparation method of tulathromycin. The method comprises protecting a 2-hydroxyl group of demethyl azithromycin through 4-nitrobenzyl chloroformate, carrying out oxidation and epoxidation on a 4"-hydroxyl group, and carrying out deprotection and 4"-epoxy nucleophilic addition through n-propylamine to obtain tulathromycin. Comprised with the prior art, the preparation method has simple processes, mild conditions and a high yield, is free of palladium-carbon hydrodeprotection and is conducive to industrial production.

The provided preparation methdo for cyclic aliphatic carbonate comprises: protecting two hydroxyl groups of the pentaerythritol to let another couple of hydroxyl react with ethyl chloroformate; further, ring-opening polymerizing or copolymerizing with aliphatic cyclic ester, removing the protection, and obtaining the product. This cyclic esters is fit to biodegradation without toxin, can connect the drug and active short peptide to improve the polymer bio- compatibility and bio-compatibility, and has wide application.

The invention discloses a preparation method of dabigatran etexilate mesylate, and belongs to the technical field of medicine. The preparation method comprises the following steps: taking 3-[(3-amino-4-methylaminobenzoyl)pyridine-2-ylamino]ethyl propanoate and N-(4-cyanphenyl)amino acetic acid as the raw materials to synthesize an intermediate (S3); making the intermediate (S3) carry out ring-closure reactions to generate an intermediate (S4); subjecting the intermediate (S4) to acid splitting in the presence of a hydrogen chloride-ethanol solution at first, then carrying out ammonification in the presence of ammonia water to generate an intermediate (S5); carrying out reactions between the intermediate (S5) and n-hexyl chloroformate under an alkaline condition to generate an intermediate (S6); dissolving the intermediate (S6), and finally carrying out reactions between the intermediate (S6) and methylsulfonic acid to obtain dabigatran etexilate mesylate. The preparation method has the advantages of simpleness, controllable and mild conditions, high yield, high product purity, stable product property, and suitability for industrial production.

The invention relates to a preparation method of 2'3'-di-O-acetyl-5'-desoxy-5-fluoro-N4-(pentyloxycarbonyl)cytidine, belonging to the technical field of medicine. The compound is an important intermediate of Capecitabine. The preparation method comprises the following step: by using anhydrous sodium carbonate or anhydrous potassium carbonate as alkali, quaternary ammonium salt as a phase-transfer catalyst and 4-substituted-pyridine as a catalyst, carrying out amidation reaction on 2'3'-di-O-acetyl-5'-desoxy-5-fluorocytidine and amyl chloroformate to obtain the 2'3'-di-O-acetyl-5'-desoxy-5-fluoro-N4-(pentyloxycarbonyl)cytidine. The invention adopts the anhydrous sodium carbonate or anhydrous potassium carbonate instead of the high-toxicity organic alkali pyridine, and obtains ideal yield and product purity. The method has the advantages of accessible raw materials, low cost, small environmental hazard, high safety and reliability, short reaction time and good product quality.

Belonging to the technical field of chemical product synthesis and beneficiation reagent production, the invention in particular relates to a synthesis process for ethoxy carbonyl isothiocyanate. The process includes: dissolving 45 parts of 99% sodium thiocyanate in 80 parts of water, adding 0.55 part of polyethylene glycol with an average molecular weight of 200 into the solution, lowering the temperature of the solution to less than 10DEG C, adding 54.8 parts of 99% ethyl chloroformate slowly into the reaction system under stirring, controlling the reaction temperature not higher than 15DEG C, and carrying out stirring reaction for 3h, at the end of the reaction, adding 30 parts of water, performing stirring for 10min, then conducting standing for 1h, separating a lower layer water phase so as to obtain an upper layer oily liquid, i.e. N-ethoxy carbonyl isothiocyanate. The ethyl chloroformate based product yield is 83.42%, the environmental pollution is reduced, energy consumption is also lowered, and the catalyst dosage is reduced.

The invention discloses an organic chemical synthesis method, in particular a method for chemically synthesizing evodiamine. Indole acetonitrile is taken as a raw material, and the method comprises the following steps of: performing catalytic hydrogenation on palladium carbon to prepare tryptamine; mixing with ethyl formate to form solution for a formylation reaction, and dissolving the reactants in solution of dichloromethane; adding trifluoroacetic acid for cyclization, and preparing another intermediate in a reflux state from N-methylanthranilic acid and excessive ethyl chloroformate; and finally, subjecting two intermediates to condensation reaction in a non-polar solvent system. The method for chemically synthesizing the evodiamine has the advantages of rich raw material source, low price of the raw material, capacities of improving the yield and fulfilling the aim of reducing the production cost by optimizing reaction conditions, environmental friendliness and suitability for large-scale industrial production. The product can be widely applied to pharmaceutical industry.

The invention provides a cyclic aliphatic carbonate monomer including 2'-benzyloxygenamide trimethylene carbonate and 2-methyl-2-benzyloxygenamide trimethylene carbonate and the polymer and the preparation method thereof. The raw material for the preparation of the two monomers is 2-amino-1,3-propanediol and 2-methyl-2-amino-1,3-propanediol, the amino group is protected, and the hydroxyl group at two ends and ethyl cacodylic acid chloroformate react to produce the monomer. The polymer with the amino at the protective side is obtained by the homopolymerization of the monomer or the copolymerization of the monomer and the aliphatic cyclic ester, and then the polymer with the side amino is obtained after escaping the protection of the polymer. The functional side amino of the polymer can be loaded with the drug molecules and the bioactive peptide by the covalent bond and the ionic bond. Thereby the invention can be applied in the fields of the drug controlled release, the gene therapy and the tissue engineering.

The present invention provides a new crystal form of mianserin hydrochloride, a detection method and applications, and relates to a traditional Chinese medicine and Western medicine preparation for depression, especially to applications of a compound drug prepared from a Western medicine mianserin hydrochloride adopted as the main component and Chinese herbs in treatment of depression. According to the mianserin hydrochloride, benzaldehyde and ethanolamine are adopted as starting raw materials and are subjected to chemical combination to obtain an intermediate I, the intermediate I reacts with styrene oxide to obtain an intermediate II, the intermediate II and thionyl chloride are subjected to chemical combination under an alkaline condition to obtain an intermediate III, the intermediate III, o-aminobenzyl alcohol and fumaric acid are subjected to chemical combination to obtain an intermediate IV, an intermediate V is obtained from the intermediate IV under the action of concentrated sulfuric acid and sodium carbonate, the intermediate V reacts with ethyl chloroformate under an alkaline condition to obtain an intermediate VI, the intermediate VI reacts with formaldehyde and formic acid to obtain an intermediate VII, and the intermediate VII is acidified with hydrochloric acid-ethyl acetate to obtain the mianserin hydrochloride. The new crystal form of the mianserin hydrochloride of the present invention has characteristics of significant treatment effect, symptom and root cause treatment, and wide application prospets.

The invention relates to the field of chemical synthesis of an insect sex pheromone intermediate, and particularly relates to a synthesis method of a laspeyresia pomonella sex pheromone intermediate (2E, 4E)-2,4-hexadienol acetate. According to the method provided by the invention, sorbic acid is used as a start material and generates an active acid anhydride with ethyl chloroformate; the active acid anhydride generates (2E, 4E)-hexadiene-1-ol in a reducing system of hydroboron anion reducing agent/inorganic aqueous alkali; and (2E, 4E)-2,4-hexadienol acetate is finally obtained through an esterification reaction. The synthesis method provided by the invention has the advantages of easily available raw materials, mild reaction conditions, convenience in operation, low requirements for equipment pipelines, high product yield and simple after-treatment, and is environment-friendly and suitable for large-scale industrial production.

The invention relates to the field of pharmaceutical chemistry, in particular to a preparation method of 2'-3'-bis-O-acetyl-5'-deoxy-5-fluoro-N4-[(pentyloxy)carbonyl]cytidine; the method comprises: reacting a compound of formula IV as a raw material with n-amyl chloroformate under the action of K3PO4 to obtain the compound of formula V, 2',3'-bis-O-acetyl-5'-deoxy-5-fluorine-N4-[(pentyloxy)carbonyl]cytidine. The invention also provides application of the method in the preparation of capecitabine. The preparation method has the advantages that reaction yield can be significantly increased, product purity is high, reaction conditions are mild, the use of pyridine is avoided, pyridine residue in the product is avoided, and the method is suitable for industrial production of medicine.

The present invention discloses a kind of L-menthol glycol carbonic ester synthesizing process. In the first step, menthol and ethyl chloroformate are reacted at 60 deg.c for 9-11 hr in the presence of catalyst pyridine or triethylamine to prepare to prepare L-menthol ethanol carbonic ester. In the second step, L-menthol ethanol carbonic ester and glycol produce alcohol exchange reaction of 10-15 hr to obtain L-menthol glycol carbonic ester at 125 deg.c and in the presence of catalyst MCM-41-TBD or HIGH-TDB. The present invention has the advantages of no use and production of phosgene and the catalyst MCM-41-TBD or HIGH-TDB used in the second step with high catalytic activity and capable of being reused.

The invention discloses a 4-methyl-2-nitroaniline synthesis method, which comprises: carrying out amino protection with ethyl chloroformate by using 4-methylaniline as a raw material to generate N-(p-toluene)ethyl carbamate; adding an oxidant and a copper salt catalyst, and carrying out a reaction for a certain time at a temperature of 50-120 DEG C in a reaction solvent by using a nitroso-containing compound as a nitrating agent to prepare a corresponding protected o-nitro-p-toluidine; and carrying out hydrolysis to obtain the target product. According to the present invention, the method hasadvantages of simple preparation process, mild reaction condition, high yield and environment protection.

The invention discloses a ciprofloxacin C3 amide derivative, a preparation method thereof and an application. The ciprofloxacin C3 amide derivative is provided with a structure as shown in a formula (I). Ciprofloxacin hydrochloride is added into excessive methylene dichloride, triethylamine is dripped to adjust the pH (potential of hydrogen) of reaction liquid to be 7.5-8.5, an appropriate amount of ethyl chloroformate is added, the reaction liquid is subjected to return flow agitation at the temperature of 20 DEG C and is clear, triethylamine is dripped into the reaction liquid so that the pH of the reaction liquid is 7.5-8.5, arylamine is added, return flow is continued for 1-2 hours, and the reaction liquid is cooled, reduced pressure distillation and concentration to obtain a target product. The ciprofloxacin C3 amide derivative has good sonodynamic activity and is obviously superior to ciprofloxacin in terms of microwave synergistic antibacterial effect.

The invention relates to a nitration method having the following principles: a phosgene species is converted with two equivalent silver nitrates into a double-mixed anhydride of carbonic acid and nitric acid, known here as carbonic acid dinitrate (I). Said operation is carried out in situ, and the formed dinitrate decomposes spontaneously. In addition to carbon dioxide, nitrate ions and nitronium ions are formed, said ions comprising electrophiles which are necessary for nitration. The solution which is used is acetonitrile, and is insignificant if the alcohol species is dissolved or suspended. The necessary equivalent silver nitrates are introduced into the system and optionally heated or cooled to the desired temperature. Subsequently, the acid chloride is introduced slowly, drop by drop or slowly little by little. Phosgene, diphosgene, triphosgene and chloroformic acid ester can be used as carbonic acid dichloride and monochloride, and their thiocarbonic acid analogues. A brown colouration and precipitated silver chloride display the formation of the carbonic acid reactants, said brown colouration rapidly discolouring due to an immediate reaction of the nitronium ions with the substrate with is to be nitrated. Towards the end of the addition of phosgene, the brown colouration remains for longer and longer until it no longer disappears. Then, it is stirred for another hour at room temperature. In the event of high acid-sensitive educts, non-nucleophilic nitrogen bases such as DBU can be added to the system in order to intercept the formation of nitric acid.

The invention provides a method for preparing 2-ethylhexyl chloroformate. The method comprises a step of reacting isooctyl alcohol with phosgene by using multiple stages of reaction kettles which areconnected in series. By adopting a micro-negative pressure system, hydrogen chloride generated by the reaction can be transferred in time, and unreacted phosgene in one reaction kettle can enter the next-stage reaction kettle for further reaction, so the utilization rate of phosgene and the conversion rate of isooctyl alcohol are improved, reaction time is greatly shortened, and industrial application value is relatively high.

The invention discloses a preparation method of a chiral intermediate for synthesizing statins. The preparation method comprises the following steps: 1, in the presence of a solvent, enabling (3R)-3-[(t-butyldimethylsilane)oxy]-glutarate monoester and 4-nitrophenyl chloroformate to react with alkali so as to obtain 1,5-p-nitrocarbobenzoxyalkyl-(3S)-3-[(t-butyldimethylsilane)oxy]-glutarate diester; 2, in the presence of a solvent, enabling triphenyl methyl phosphonium bromide to react with alkali and then react with 1,5-p-nitrocarbobenzoxyalkyl-(3S)-3-[(t-butyldimethylsilane)oxy]-glutarate diester to obtain a target product, namely (3R)-3-[(t-butyldimethylsilane)oxy]-5-oxo-6-triphenylphosphine caproate. According to the preparation method disclosed by the invention, the reaction process is more stable, the raw material utilization ratio is relatively high, and the yield is obviously improved. More importantly, due to the reduction of impurities, the product can obtain purity according with industrial production through simple crystallization operation, so that the production efficiency is greatly improved, the cost is saved, and the environment friendliness is ensured at the same time.

The invention discloses a preparation method of thymopeptide-5, comprising the following steps: using tyrosine benzyl ester hydrochloride as a starting material; using N-methyl morpholine as a catalyst; adopting alkyl chloroformate as an activating agent and activating protected amino acid to form high-activity mixed anhydride which reacts with exposed amino acid or peptide of an amino end. The high-purity thymopeptide-5 is prepared by the steps: dipeptide combination, kyrine combination, tetrapeptide combination, pentapeptide combination, crude generation and purification. The method simplifies a technology, has little three-waste pollution and is convenient to implement industrially.

The invention discloses a new synthesizing method of Azidothimidine carbonic cholesterol ester (or other esters of sterol) as drug primer, which is characterized by the following: adopting Azidothimidine and cholesterol to form chloroformate cholesterol ester; fitting for multiple agents; establishing internal and external analytic method; detecting medical kinetics in the mouse; obtaining the product with half-decay time at 4.9h; lengthening AZT acting time; reducing side-effect; targeting AIDS enriched organs and tissues.