157 results about "Cyclopropanation" patented technology

A method of producing 6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one comprising subjecting a cyclopropane compound of the formula (1):

(wherein, R¹ represents an alkyl group, R² represents an alkyl group having carbon atom(s) of 1 to 10, a haloalkyl group having carbon atom(s) of 1 to 10, or an aryl group having carbon atoms of 6 to 10 optionally substituted by an alkyl group having carbon atom(s) of 1 to 10, and when R² represents the alkyl group, R¹ and R² are optionally the same or different each other.) to any of the following reactions a), b) and c):

• • a) an acid treatment reaction after an alkali hydrolysis reaction
  • b) an acid hydrolysis reaction
  • c) an enzyme hydrolysis reaction , then, removing an aqueous layer.

Chiral ruthenium catalysts comprising salen and alkenyl ligands are provided for stereoselective cyclopropanation, and methods of cyclopropanation are provided. The chiral ruthenium catalyst is prepared in situ by combining an alkenyl ligand, a deprotonated chiral salen ligand, and a ruthenium (II) metal. A preferred catalyst is prepared in situ by combining 2,3-dihydro-4-venylbenzofuran, deprotonated 1,2-cyclohexanediamino-N,N′-bis(3,5-di-t-butyl-salicylidene) and RuCl₂(p-cymene)]₂.

Chiral ligands and transition metal complexes based on such chiral ligands useful in asymmetric catalysis are disclosed. The chiral ligands include phospholanes, P,N ligands, N,N ligands, biphenols, and chelating phosphines. The ferrocene-based irridium (R,R)-f-binaphane complex reduces imines to the corresponding amines with 95-99.6% enantioselectivity and reduces beta-substituted-alpha-arylenamides with 95% enantioselectivity. The transition metal complexes of the chiral ligands are useful in asymmetric reactions such as asymmetric hydrogenation of imines, asymmetric hydride transfer reactions, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, allylic alkylation, cyclopropanation, Diels-Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition and epoxidation reactions.

Chiral ligands and transition metal complexes based on such chiral ligands useful in asymmetric catalysis are disclosed. The chiral ligands include (R,S,S,R)-DIOP*. The ruthenium complex reduces enamide to the corresponding amine with up to 99% enantioselectivity. The transition metal complexes of the chiral ligands are useful in asymmetric reactions such as asymmetric hydrogenation, hydride transfer, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, hydrocarboxylation, isomerization, allylic alkylation, cyclopropanation, Diels-Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition and epoxidation reactions.

The invention relates to a method for preparing a hydrochloride of 6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazole. The method is to subject 2,4-difluorophenyl(4-piperidinyl) ketoxime or a hydrochloride thereof to cyclopropanation and salifying in an aprotic solvent containing an alkali metal hydroxdide, wherein the molar ratio of the 2,4-difluorophenyl(4-piperidinyl) ketoxime or a hydrochloride thereof to the alkali metal hydroxide is 1 to between 1 and 3. The method can effectively prevent F atoms on para positions from participating in the reaction and avoid the production of a dipolymer (V), thereby avoiding the production of a dipolymer (VI) during the following preparation of risperidone. The method crystallizes crystals of a target substance directly by salifying, thereby solving the problems of use of a plurality of kinds of organic solvents, complex operation and low yield due to the extraction by toluene, condensation, and crystallization of petroleum ether. The yield rate of the target substance is more than 80 percent, and the purity of target substance is more than 99 percent.

A carried catalyst used for cyclopropanizing 2,5-dimethyl-2,4-hexadiene contains the active component (20-90%) chosen from Fe, Ca, Ni, Ca, Zn, Cr, Mo or Ti, the assistant (0.1-5%) chosen from L, Na or K, and the carrier chosen from alumina silica gel and activated carbon. It is prepared through premodifying carrier, and immersing while adding active component and the organic compound containing hydroxy or carboxyl group and oxygen. Its advantages are low dosage, high output rate, little coking and easy separation.

The present invention pertains to the use of engineered variants of enzyme CYP102A, also known as P450-BM3, for cyclopropanation of olefins containing electron-withdrawing groups. One exemplary enzyme variant, referred to as BM3-HStar, contains five mutations away from wild-type P450-BM3, and demonstrates high activity towards cyclopropanation of olefinic substrates using ethyldiazoacetate (EDA) and other carbene transfer reagents. Products of these reactions are potential precursors of levomilnacipran derivatives, a class of compounds that have been shown to be selective inhibitors of monoamine transporters. In addition, cyclopropanation reactions with the P450-BM3 enzyme variants of the invention can be conducted in whole cells expressing the enzyme variants and can proceed under aerobic conditions.

An abscisic acid (1) is a plant hormone widely existing in a plant and has important physiological function, however, the application range is limited by the high-speed photo-isomerization characteristics. A bioisosteres cis 2, 3-cyclopropanated abscisic acid analogue of the abscisic acid is compounded through 2, 3-cyclopropanation, and the photostability is four times as that of the abscisic acid.

The invention discloses a method for preparing (1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine. The method comprises the following steps: carrying out a Fuke acyl reaction on 3,4-difluorobromobenzene (compound 2) which serves as a raw material and chloroacetyl chloride under conditions of lewis acid and certain temperature to obtain a compound 3; carrying out stereoselective reduction to obtain a compound 4; carrying out cyclization, olefination, hydrolyzation and debromination to obtain a compound 8; and preparing amide, and carrying out Hoffmann elimination to obtain a target compound 1. According to the method, the traditional preparation process is improved, the (1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine can be effectively, simply and conveniently prepared, the total yield is relatively high, the stereoselection is relatively high, and the intermediate in each step is easily purified and stored. The reaction formula in the method is as shown in the specification.

The invention discloses a method for preparing 6beta,7beta-methylene-steride-3beta,5beta-diol, comprising the following steps of: preparing steride-4,6-dien-3beta-ol by using steride-4,6-dien-3beta-one as the raw material through a reductive reaction; preparing 4beta,5beta-epoxy steride-6-alkenyl-3beta-ol by the steride-4,6-dien-3beta-ol through epoxidation; preparing the intermediate steride-6-alkenyl-3beta,5beta-diol by the 4beta,5beta-epoxy steride-6-alkenyl-3beta-ol through a reductive ring opening reaction, and preparing the aimed compound 6beta,7beta-methylene-steride-3beta,5beta-diol by the intermediate through cyclopropanation reaction addition or directly preparing the aimed compound 6beta,7beta-methylene-steride-3beta,5beta-diol by the 4beta,5beta-epoxy steride-6-alkenyl-3beta-ol through cyclopropanation reaction. The invention has the advantages of low cost and easy availability of raw material, easy preparation of 4beta,5beta-epoxy steride-6-alkenyl-3beta-ol, high stereoselectivity for constructing 6beta,7beta-methylene structural unit, less reaction steps, simple operation and high yield, therefore, the method is suitable for industrialized production.

This invention relates to process for synthesizing S-(+)-2,2-dimethyl cyclopropane formyl amide, using penteneic acid as main raw material, after procedures of: esterification, cyclopropanization, hydrolyzation, acylation, salifying, partial crystallization and ammonolysis. advantages are: short reaction time, mild reaction condition, simple process, total yield is more than 15%, ee is larger than 95.6%.

A preparation method of 2-(o-hydroxyphenyl)cyclopropane-1-carboxylic acid is provided. With o-alkoxy cinnamic acid as a raw material, 2-(o-alkoxyphenyl)cyclopropane-1,1-ethyl dicarboxylate is obtained through pyrolysis decarboxylation, halogen addition and cyclopropanation, and then the novel tobacco spice 2-(o-hydroxyphenyl)cyclopropane-1-carboxylic acid is prepared through deestering, hydrolysis, demethylation and other steps. The raw material and reagents in the route are all commercial products, so that the raw material is easy to obtain; the reaction steps are all classic organic reactions, especially the cyclopropanation step avoids the use of expensive trimethylsulfoxonium halogen (TMSOX, wherein X is Cl, Br or I) reagents, and thus the cost of production is significantly reduced. Through process optimization, the overall yield of the reaction reaches 53%. The method has the advantages of simple operation, high synthesis yield, low costs of the raw material and the reagents, easy scale production and the like. The 2-(o-hydroxyphenyl)cyclopropane-1-carboxylic acid prepared by the method is mainly used in spice and essence industries.

The invention belongs to the field of synthesis of a metal complex, and particularly relates to a metal complex of a novel double piperidine derivative with a symmetric structure. According to the complex, under the protection of nitrogen gas, salt of corresponding metal is added into a reaction bottle provided with a reflux condensing tube; methanol is used as a solvent; the salt and the solvent are stirred until the salt is dissolved to obtain clear solution; double piperidine ligand is added and is heated under stirring until reflux occurs; after the double piperidine ligand is not available in the solution to be reacted, the solution is cooled to room temperature; the solvent is removed under reduced pressure; and residues are recrystallized to obtain the metal complex of the corresponding double piperidine derivative. The metal complex of the double piperidine derivative shows better catalytic performance in catalytic reaction such as epoxidation of olefin, asymmetric epoxidation of olefin, asymmetric addition of benzaldehyde and diethyl zinc and cyclopropanation of styrene.

Chiral ligands and metal complexes based on such chiral ligands useful in asymmetric catalysis are disclosed. The metal complexes according to the present invention are useful as catalysts in asymmetric reactions, such as, hydrogenation, hydride transfer, allylic alkylation, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, olefin metathesis, hydrocarboxylation, isomerization, cyclopropanation, Diels-Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition; epoxidation, kinetic resolution and [m+n] cycloaddition. Processes for the preparation of the ligands are also described.

The invention discloses a synthesis method of tasimelteon. The synthesis method comprises steps as follows: a compound (I) is subjected to an epoxidation reaction, and a compound (II) is obtained; the compound (II) and diethyl cyanomethylphosphonate are subjected to a ring-closure reaction under the protection of inert gas, and a compound (III) is obtained; the compound (III) is subjected to a reduction reaction, and a compound (IV) is obtained; the compound (IV) is subjected to an acylation reaction, and tasimelteon (V) is obtained. The route is simple, 4-vinyl dihydrobenzofuran is taken as a raw material and subjected to four steps of reactions including epoxidation, cyclopropanation, reduction and acylation, and the target product tasimelteon (V) is prepared. The reaction efficiency is greatly improved, the reaction steps are reduced, the operation procedures are simplified, and a new approach for synthesis of tasimelteon is provided. Besides, the method is suitable for industrial production and has great practical application value and social and economic benefits.

The present invention provides methods for catalyzing the conversion of an olefin to any compound containing one or more cyclopropane functional groups using heme enzymes. In certain aspects, the present invention provides a method for producing a cyclopropanation product comprising providing an olefinic substrate, a diazo reagent, and a heme enzyme; and admixing the components in a reaction for a time sufficient to produce a cyclopropanation product. In other aspects, the present invention provides heme enzymes including variants and fragments thereof that are capable of carrying out in vivo and in vitro olefin cyclopropanation reactions. Expression vectors and host cells expressing the heme enzymes are also provided by the present invention.