177793-80-5

Basic information

• Product Name: (3S)-N-[[(1S)-1,2,3,4-Tetrahydro-1-naphthalenyl]Methyl]-1-azabicyclo[2.2.2]octan-3-aMine
• Synonyms: (3S)-N-[[(1S)-1,2,3,4-Tetrahydro-1-naphthalenyl]Methyl]-1-azabicyclo[2.2.2]octan-3-aMine;[S-(R*,R*)]-N-[(1,2,3,4-Tetrahydro-1-naphthalenyl)Methyl]-1-azabicyclo[2.2.2]octan-3-aMine;(3S)-N-[[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]methyl]-1-azabicyclo[2.2.2]octan-3-amine
• CAS NO: 177793-80-5
• Molecular Formula: C18H26N2
• Molecular Weight: 270
• Product Categories: Amines;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 177793-80-5.mol
• Article Data: 6

Chemical Properties

• Appearance: /
• CAS DataBase Reference: (3S)-N-[[(1S)-1,2,3,4-Tetrahydro-1-naphthalenyl]Methyl]-1-azabicyclo[2.2.2]octan-3-aMine(CAS DataBase Reference)
• NIST Chemistry Reference: (3S)-N-[[(1S)-1,2,3,4-Tetrahydro-1-naphthalenyl]Methyl]-1-azabicyclo[2.2.2]octan-3-aMine(177793-80-5)
• EPA Substance Registry System: (3S)-N-[[(1S)-1,2,3,4-Tetrahydro-1-naphthalenyl]Methyl]-1-azabicyclo[2.2.2]octan-3-aMine(177793-80-5)

Safety Data

• Hazardous Substances Data: 177793-80-5(Hazardous Substances Data)

Upstream product

• 177793-79-2 N-(1-azabicyclo[2.2.2]oct-3-yl)-1,2,3,4-tetrahydronaphthalen-1-ylcarboxamide 
• 177793-79-2 N-(1-azabicyclo[2.2.2]oct-3S-yl)-1,2,3,4-tetrahydronaphthalene-1S-carboxamide 
• 85977-52-2 (S)-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid 
• 1914-65-4 tetralin-1-carboxylic acid 
• 50341-99-6 1,2,3,4-tetrahydronaphthalene-1-carbonyl chloride 
• 18278-24-5 (S)-(-)-1,2,3,4-tetrahydro-1-naphthaldehyde 
• 120570-05-0 (S)-3-aminoquinuclidine 
• 80096-46-4 (1,2-dihydronaphthalen-4-yl)methanamine hydrochloride 
• 1193-65-3 3-quinuclidinone hydrochloride 

Downstream Products

• 135729-60-1 palonosetron 
• 135755-51-0 palonosetron hydrochloride 

Relevant articles and documents

Preparation method of high-purity palonosetron hydrochloride

The invention discloses a preparation method of high-purity palonosetron hydrochloride. A synthesis method is as follows: taking 1,2,3,4-tetrahedro-naphthoic acid as a starting raw material, taking quinine as a resolving agent to obtain chiral(S)-1,2,3,4-tetrahedro-naphthoic acid, acylating the chiral(S)-1,2,3,4-tetrahedro-naphthoic acid by using oxalyl chloride, and then reacting with (S)-3-aminoquinuclidine ammonia salt to obtain amide compound; concentrating, adding water to dilute, adding alkali to adjust pH value to obtain (R)-N-((S)-3-quinine)-1,2,3,4-tetralyl-1-formamide; performing reduction reaction on an intermediate under the existence of the sodium borohydride and boron trifluoride diethyl etherate so as to obtain (R)-N-(1-((S)-1,2,3,4-tetralyl)methyl)-3-quinine amine, continuously reacting with the triphosgene and boron trifluoride diethyl etherate, salting, extracting and regulating the pH value to obtain a crude product of the Palonosetron after the reaction is completed; and salting and refining the crude product in isopropanol so as to obtain the Palonosetron Hydrochloride with high purity. The preparation method not only solves the problem that the palonosetron hydrochloride is low in yield and unstable in process for a long time, but also adopts class-three solvent ethyl acetate to extract in the synthesis of each step, the invention is in favor of the environmental protection, and convenient for solvent recycling and cost saving, and is suitable for industrial production.

A hydrochloric acid palonosetron synthesis method

The invention relates to a new synthetic method of palonosetron hydrochloride, and belongs to the field of pharmaceutical organic synthesis. The synthetic method adopts racemized tetrahydro naphthoic acid as a raw material; a reaction is carried out with thionyl chloride and (S)-3-aminoquinuclidine; after repeated washing, (S,S)-quinuclidine tetrahydronaphthalene carboxamide is obtained; the amide is reacted with sodium borohydride and boron trifluoride diethyl etherate; the product is added into a hydrochloric acid aqueous solution to obtain the palonosetron hydrochloride. According to the method, in the amide synthetic process, ethyl acetate is used as a solvent, which reduces the generation of by-products. In addition, according to the method, in the post-treatment process, impurities are removed by phase transfer, which increases product optical purity; through repeated washing, other impurities generated in the reaction are removed, and high-purity product is obtained.

A hydrochloric acid palonosetron production method

The invention belongs to the field of organic synthesis, and particularly relates to a production method of high-purity and high-yield palonosetron hydrochloride. Chiral compounds, namely, (S)-(-)-1,2,3,4-tetrahedro-naphthoic acid and S-3-aminoquinuclidine, are taken as raw materials, and an intermediate is obtained; the intermediate has a reduction reaction in the presence of NaBH4 and BF3*CH3OH, a product is added to a hydrochloric acid aqueous solution for a reflux reaction after the reaction, and a transparent oily substance is obtained through extraction after the reflux reaction; toluene is added to the substance, a toluene solution of triphosgene is dropwise added again at the temperature ranging from 10 DEG C to 15 DEG C, white solids are separated out, a reaction is performed under the condition of heating reflux, and the toluene solution of the triphosgene is dropwise added again under the reflux condition; then a system is cooled to the temperature ranging from 10 DEG C to 15 DEG C, BF3*CH3OH is added, the system is added to water and the hydrochloric acid aqueous solution at the reflux temperature after addition, then a reflux reaction is performed at the heating reflux temperature, and then a crude product is obtained through washing, extraction and crystallization; the crude product is dissolved in acetone, repeated crystallization is performed after dissolution, and the refined palonosetron hydrochloride is obtained. Steps are simple and convenient, reaction conditions are mild, and the production method is easy to operate and suitable for industrial production.