41results about How to "React Operational Security" patented technology

The invention discloses a synthesis method of metaraminol bitartrate, and in particular provides a method for synthesizing metaraminol bitartrate by using a chiral catalysis method. The synthesis method comprises the steps: catalyzing a chiral addition reaction of hydroxybenzaldehyde and nitroethane by using a chiral catalyst system consisting of cinchona alkaloid, copper acetate hydrate and less imidazole to obtain an addition product with a dominant required spatial configuration, and then reducing nitro by using hydrogen in the presence of Pd-C to obtain amine to obtain aramine, and salifying the aramine with L(+)-tartaric acid to obtain a final product metaraminol bitartrate. According to the synthesis method, an enzyme catalyst is prevented from being used, a raw material of the synthesis reaction is easily available, the chiral catalyst is easily purchased or prepared self, the synthesis steps are relatively less, the chiral control efficiency is higher, the enantioselectivity is high, the yield is good, the reaction operation is easily controlled, and is safe and reliable, and the foundation is laid for the later industrialized amplification production.

The invention discloses a synthetic method of pregabalin. According to the synthetic method, isovaleraldehyde and cyanoacetic alkyl ester are used as starting materials; condensation reaction, Michael addition reaction, hydrolysis reaction, amidation reaction and the like are carried out successively to obtain 3-(carbamoyl methyl)-5-methyl-hexanoic acid; and resolution and Hofmann elimination are carried out to obtain pregabalin. The greatest improvement of the synthetic method is to carry out the hydrolysis reaction and the amidation reaction under the condition of near-critical water. Thus, addition of a catalyst is avoided, and yield of the reaction is raised. In addition, a flow reactor can be applied to the reaction so as to obtain a better reaction effect.

The invention provides a preparation method of solithromycin. The method comprises the following steps: performing fluorination reaction on a compound II to generate a compound III; forming a butt joint on the compound III and 4-azidobutylamine to form an oxazole ring compound VI; and performing ring-closing reaction on the compound VI and 3-aminophenylacetylene to obtain the solithromycin I. The method abandons the explosive and hazardous azido intermediate oxidization in the prior art, so the reaction operation is safer. Especially, it is pleasantly surprising that in the process of preparing oxazole-ring and five-membered ring triazoles, since the reactant solubility is higher, the reactant conversion rate is high, and the side reactions are fewer; and thus, the method lowers the production cost, is beneficial to environmental protection and suitable for industrial production, and has great application value.

The invention provided a method for preparing solithromycin. The method comprises the following steps: a compound II is subjected to a fluorination reaction, so that a compound III is produced, and the compound III docks with an amino group in a side chain of a compound IV five-member ring triazole (1-(4-aminobutyl)-4-(3-protected aminophenyl)-1H-1,2,3-triazole), so that a compound V containing an oxazole ring is formed; and the compound V is subjected to corresponding de-protection or reduction to form an amino group, so that solithromycin I is obtained. The method for preparing the solithromycin gets rid of easy-explosion dangerous oxidation and fluorination reactions of azido intermediates in the prior art, and reaction operation is more safe; and it is surprised that when the oxazole ring triazole and the five-member ring triazole are prepared, solubility of reactants is high, so that the conversion rate of the reactants is high, side reactions are less, and the production cost is reduced. The method facilitates environmental protection, is suitable for industrialized production, and has a large application value.

The invention relates to a method for efficiently synthesizing alpha, beta-unsaturated aldehyde. A series of alkynes can be efficiently and rapidly converted into alpha, beta-unsaturated aldehydes through a hydroformyl transfer reaction between simple alkyl aldehydes and alkynes by using cheap and easily available n-butyraldehyde as a donor of hydroformyl. Compared with a traditional hydroformylation reaction system, the method does not need to use flammable and combustible synthesis gas, does not need to use a special device to contain the synthesis gas, adopts commercially available catalysts and ligands, is simple and convenient to operate, mild in condition and low in cost, and thoroughly inhibits side reaction products such as saturated aldehyde and alkyne hydrogenation products; andthe compound has specific chemoselectivity and excellent regioselectivity and stereoselectivity, and has huge application potential.

The invention belongs to the technical field of drug synthesis, and discloses a preparation method of metaraminol bitartrate, which comprises the following steps: under an alkaline condition, a compound V and a compound IV are subjected to a Henry reaction under the action of a metal catalyst and a chiral ligand to obtain a compound III, the compound III is subjected to catalytic hydrogenation to obtain a compound II, and the compound II is subjected to recrystallization to obtain metaraminol bitartrate. And salifying the compound II and L-tartaric acid to obtain metaraminol bitartrate I, wherein the chiral ligands are a compound VI and a compound VII. The method can effectively control the three-dimensional configuration in the production process, can obviously improve the product quality, and is simple in production process, high in yield, low in cost and suitable for industrial production.

The invention discloses a preparation method of sugammadex sodium. The method comprises the following steps: taking gamma-cyclodextrin as a raw material, reacting gamma-cyclodextrin with 3-mercaptopropionic acid substituted ester under the action of a phosphine reagent and an azo reagent to generate sugammadex ester; and hydrolyzing the sugammadex ester and an alkaline reagent in a solvent at a certain temperature to obtain the target product sugammadex sodium. The preparation method of sugammadex sodium is mild in reaction, a gamma-cyclodextrin perhalogenation reaction process is omitted, theoperation is simple, convenient and time-saving, the yield of the obtained target product is high, and the method is suitable for industrial scale-up production.