180272-14-4

Usage

InChI:InChI=1/C23H26N2O2/c26-23(27-21-16-24-13-10-18(21)11-14-24)25-15-12-17-6-4-5-9-20(17)22(25)19-7-2-1-3-8-19/h1-9,18,21-22H,10-16H2/t21-,22-/m0/s1

Upstream product

• 180468-42-2 (S)-N-carboxylic acid ethyl ester-1-phenyl-1,2,3,4-tetrahydroisoquinoline 
• 25333-42-0 (R)-quinuclidin-3-ol 
• 52250-50-7 1-phenyl-3,4-dihydroisoquinoline 
• 3278-14-6 N-phenethylbenzamide 
• 22990-19-8 (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline 
• 1251905-45-9 methyl (1S)-1-phenyl-3,4-dihydro-2(1H)-isoquinoline-carboxylate 
• 124-41-4 sodium methylate 
• 20194-18-7 sodium phenyl-methanolate 
• 1203447-95-3 phenyl (S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate 
• 180468-37-5 (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydro-isoquinoline-2-carboxylate hydrochloride 
• 1229227-22-8 4-nitrophenyl (1S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 1243274-81-8 (3R)-1-azabicyclo[2.2.2]oct-3-yl 4-nitrophenyl carbonate 
• 1262506-09-1 solifenacin succinate 
• 627-11-2 2-Chloroethyl chloroformate 

Downstream Products

• 180468-37-5 Solifenacin hydrochloride 
• 1172614-17-3 solifenacin hydrogen adipate 
• 180272-28-0 (1'S,3R)-3-[[(1'-phenyl-1',2',3',4'-tetrahydro-2'-isoquinolyl)carbonyl]oxy]quinuclidine 1-oxide 
• 865813-75-8 (-)-(3R)-quinuclidin-3-yl (1R)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate naphthalene-2-sulfonate 
• 1354548-49-4 1-azabicyclo[2.2.2]oct-8-yl (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate fumarate 

Relevant academic research and scientific papers

Synthesis process of solifenacin succinate

The invention discloses a synthesis process of solifenacin succinate, and relates to the technical field of medicines. The preparation method comprises the following steps: step 1, reacting (R)-quinuclidin-3-ol (B) with a reaction substance to generate (R)-quinuclidin-3-yl carbonochloridate (C); step 2, enabling (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline (A) to react with (R)-quinuclidin-3-yl carbonochloridate (C) to generate solifenacin (D); and step 3, using the solifenacin (D) to prepare the solifenacin succinate. After the technical scheme is adopted, the method has the beneficial effects that in the synthesis process, the problem of low conversion rate caused by direct ester exchange reaction is avoided, meanwhile, the probability of reversible reaction caused by nucleophilic intermediate products generated in the condensation process is also reduced, and the reaction is greatly promoted, so that the yield of solifenacin succinate is increased, the reaction conditions are mild, the operation is simple, the operation procedures are reduced, and the method is suitable for large-scale production.

Asymmetric synthesis method for preparation of solifenacin

The invention relates to an asymmetric synthesis method for preparation of solifenacin and specifically, discloses a preparation method of solifenacin. The method comprises that ortho-substituted aldehyde as a raw material undergoes a reaction under catalysis of rhodium and a chiral sulfoxide-olefin ligand to produce a key intermediate for high enantioselective addition, and the intermediate is further functionalized and cyclized to form solifenacin. The method is easy to operate, needs mild reaction conditions and has high efficiency and high selectivity.

Solifenacin succinate new preparation method

The present invention relates to a solifenacin succinate new preparation method which mainly comprises the following steps: 1) formula III compound (R)-(-)-quinuclidin-3-ol and formula IV compound N,N,-N,N-carbonyldiimidazole are reacted to obtain formula V compound (R)-imidazole-1-carboxylic acid-1-azabicyclo[2,2,2] octyl ester; 2) the formula V compound (R)-imidazole-1-carboxylic acid-1-azabicyclo[2,2,2] octyl ester is reacted with formula VI compound (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline to obtain a formula II solifenacin alkaline body; 3) the formula II solifenacin alkaline body isreacted with succinic acid, refined and purified to obtain formula I solifenacin succinate. The preparation method has the advantages that the yield of the solifenacin succinate is high and the purityis high, and the process is simple and suitable for industrial production.

A succinic acid thorley that new preparation method

The invention relates to a preparation method of succinic acid solifenacin, and belongs to the technical field of medicinal raw material preparation. According to the technical scheme, the preparation method of the novel succinic acid solifenacin is characterized in that R-3-quinuclidinol, S-1-phenyl-1, 2, 3, 4-tetrahydro naphthalene are used as raw materials, a reaction product of triphosgene and substituted phosphine oxide is used as a condensing agent, the solifenacin is prepared through a one-pot method, and then the succinic acid solifenacin is obtained through salifying. The preparation method of the succinic acid solifenacin has the beneficial effects that the operation is simple, reaction conditions are mild, and the preparation method is suitable for industrial amplification production.

A process for the preparation of new thorley that succinic acid

The invention relates to a method for preparing a solifenacin succinate ((3R)-1-azabicyclo [2.2.2] octane-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2-(1H)-carboxylate succinate). The method comprises the following steps: 1) preparing a compound (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline carboxylic acid ethyl ester of formula III from a compound (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline, serving as a raw material, of formula IV; 2) synthesizing a compound (3R)-1-azabicyclo [2.2.2] octane-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2-(1H)-carboxylate of formula II in an ionic liquid by using the compound (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline carboxylic acid ethyl ester of formula III; and 3) salifying the compound (3R)-1-azabicyclo [2.2.2] octane-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2-(1H)-carboxylate of formula II in an organic solvent to obtain the compound solifenacin succinate ((3R)-1-azabicyclo [2.2.2] octane-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2-(1H)-carboxylate succinate) of formula I. The preparation method has the advantages that the process is simple, the method is suitable for industrialized production, the yield of the product is high and the purity of the product is high.

After-treatment for solifenacin and method for preparing succinic acid solifenacin

The invention discloses an after-treatment method for solifenacin. The method comprises the steps that strong acid is slowly dripped into total synthesis liquid of solifenacin, after a pH value is adjusted to be 1.0-2.0, temperature is raised, water is added, and an extracting agent is used for extraction; after a water phase is cooled, a saturated sodium carbonate solution is added to alkalinity, dichloromethane is added to carry out graded extraction, extract liquor is washed with water, and a drying agent is added for drying, so that a dry product is obtained; the dry product is steamed at low temperature to be dry to obtain an oily substance solifenacin. By optimizing the after-treatment technology, isopropyl ether and dichloromethane are only used in the after-treatment technology of solifenacin, types of solvent are reduced, operation and recycle are facilitated, and cost is saved greatly. Strong base or strong acid is not used in the alkali efflorescence process of hydrochloric acid solifenacin, a saturated NaCO3 solution is used, the reaction is mild, temperature can be controlled easily, most importantly, generation of isomers is greatly reduced, and the content of the isomers of a non-structure type (1S and 3R) is reduced.

PROCESS FOR PREPARING (1S)-1-PHENYL-3,4-DIHYDRO-2(1H)-ISOQUINOLINE-CARBOXYLATE

A process for preparation of (1S)-1-phenyl-3,4-dihydro-2(1H)-isoquinoline-carboxylate (Formula I), comprising reacting (1S)-1-phenyl-3,4-dihydro-2(1H)isoquinoline (Formula II) with carbon dioxide and an alkylating agent R-LG in the presence of a base to obtain the compound of Formula I in an organic solvent. In Formula I and II, R is an alkyl or a substituted alkyl; LG is a leaving group.

PROCESS OF PREPARING SOLIFENACIN OR SALT THEREOF, AND NOVEL INTERMEDIATE USED IN THE PROCESS

Disclosed herein is a method of preparing solifenacin or a salt thereof, including the steps of: (a) reacting (R)-quinuclidinol with bis(pentafluorophenyl)carbonate in an organic solvent to prepare a solifenacin intermediate, (3R)-1-azabicyclo[2,2,2]oct-3-yl pentafluorophenylcarbonate, and (b) reacting the solifenacin intermediate with (1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline in an organic solvent to prepare solifenacin. The method is advantageous in that high-purity solifenacin or a salt thereof can be simply and efficiently prepared with high yield using a novel intermediate.

Process for the Preparation of Solifenacin and Salts Thereof

The invention provides a new process for the preparation of solifenacin or a pharmaceutically acceptable acid addition salt thereof, comprising reacting (R)-quinuclidin-3-yl phenethylcarbamate with benzaldehyde in the presence of an acid to obtain a diast

Stereoselective Total Syntheses of Solifenacin and N -Acetyl-1-(4-chloro-phenyl)-6,7-dimethoxytetrahydroisoquinoline

A highly stereoselective synthesis of 1-aryl-1,2,3,4-tetrahydroisoquinoline drugs such as solefinacin (muscarinic acetylcholine receptor antagonist) and N-acetyl-1-(4-chlorophenyl)-6,7-dimethoxytetrahydroisoquinoline (AMPA receptor antagonist) has been accomplished using (R)-tert-butanesulfinamide as a chiral source. Chiral tetrahydroisoquinolines have been prepared through the aryl Grignard addition to chiral N-sulfinylimines followed by haloamide cyclization.