- Preparation method of raloxifene hydrochloride and intermediate thereof
-
The preparation method comprises the following steps: preparing a raloxifene hydrochloride precursor (intermediate 2) from 1-{4-[2-(piperidine-1-yl)ethyoxyl]phenyl}-2-(2-sulfydryl-4-methoxyphenyl)ethanone (intermediate 1) and 4-methoxybenzoyl halide, performing demethylation protection, and preparing raloxifene hydrochloride from the demethylated raloxifene hydrochloride precursor and hydrochloricacid. Herein, the intermediate 1 is generated by removing benzyl protection from an intermediate 3 (1-{4-[2-(piperidine-1-yl)ethoxy]phenyl}-2-(2-benzylthio-4-methoxyphenyl)ethanone) in trifluoroacetic acid through a reaction; (3-methoxyphenyl) benzyl sulfide is oxidized to generate a sulfoxide compound, and then the sulfoxide compound reacts with 1-[2-(4-ethynylphenoxy)ethyl]piperidine to generate an intermediate 3. The method has the advantages of mild reaction conditions, few side reactions, high yield, cheap reagent raw materials, easy recovery and easy preparation, and is suitable for industrial large-scale production.
- -
-
-
- Method for synthesizing D-Diphenyl formyl-tartaric acid and co-producing methyl benzoate
-
The invention provides a method for synthesizing D-dibenzoyl tartaric acid and co-producing methyl benzoate. The method comprises the following steps that S1 an organic solvent, D-tartaric acid and lewis acid are added into a reaction bottle, stirred and heated, benzoyl chloride is added dropwise, heat preservation is conducted for 30-90 minutes, a product is cooled to be at 0-5 DEG C, suction filtration is conducted, and a filter cake A and filtrate A are obtained; S2 methyl alcohol is added into the filter cake A and stirred for 30 minutes, suction filtration is conducted, and a filter cakeB and filtrate B are obtained; S3 the filter cake B is added into pure water, heating and back flowing are conducted for 1.5-2.5 hours, a product is cooled to be at 25-30 DEG C, suction filtration isconducted, the filter cake is dried, and D-dibenzoyl tartaric acid is obtained; and S4 an esterification reaction catalyst is added into the filtrate B, back flowing is conducted, alkali is added to adjust the pH value, atmospheric distillation is conducted, water is added to wash the product, vacuum rectification is conducted, and the methyl benzoate is obtained. The method has the advantages that the technology is simple, the operation is convenient, the condition is moderate, the product chromaticity is good, the method is environmentally friendly, the cost is low, the product yield is high, and the product purity is high.
- -
-
-
- A pizotifen derivative and its preparation method (by machine translation)
-
The invention discloses a pizotifen derivatives, its molecular formula is The preparation of the pizotifen derivatives raw materials used is simple, its reaction condition is easy to reach, and has a higher yield, in the reaction process also will not produce harmful substances, is a raw material and the reaction conditions are simple pizotifen derivatives. (by machine translation)
- -
-
Paragraph 0048-0050; 0058; 0060; 0070-0073; 0078-0079
(2019/02/25)
-
- Direct synthesis of 3-acylbenzothiophenes: Via the radical cyclization of 2-alkynylthioanisoles with α-oxocarboxylic acids
-
A radical cascade cyclization of 2-alkynylthioanisoles with α-oxocarboxylic acids with AgNO3 has been described. This reaction provides a novel route to directly access 3-acylbenzothiophenes from simple chemical feedstocks. In particular, the utility of the approach was demonstrated by its application to the synthesis of a polymerization inhibitor and a raloxifene precursor.
- Liu, Wei,Hu, Yao-Qian,Hong, Xiao-Yi,Li, Guo-Xing,Huang, Xiao-Bo,Gao, Wen-Xia,Liu, Miao-Chang,Xia, Yuanzhi,Zhou, Yun-Bing,Wu, Hua-Yue
-
p. 14148 - 14151
(2019/01/03)
-
- Efficient synthesis of 3-benzoyl Benzo[b]thiophenes and raloxifene via Mercury(II)-Catalyzed cyclization of 2-alkynylphenyl alkyl sulfoxides
-
The unique selective estrogen receptor modulator, Raloxifene (1), and antitubulin agent 2 were synthesized through the key intermediate, 4-methoxybenzyl 2-bromo-4-methoxyphenyl sulfoxide (6), respectively. It was found that compared with the o-sulfanyl aryl bromides, the sulfinyl group at ortho position accelerated the Sonogashira coupling reaction of aryl bromides. Thus, compound 6 was coupled with 3,4,5-trimethoxyphenyl acetylene, followed by mercury-catalyzed cyclization reaction afford compound 2 in 79% overall yield. Raloxifene (1) was prepared from compound 6 in four steps and 33% overall yield via coupling reaction with 1-trimethylsily-2-(4-tert-butyldimethylsiloxy)phenylethyne, mercury-catalyzed cyclization reaction, alkylation and demethylation.
- Wen, Shi-Ming,Lin, Cheng-Han,Chen, Chin-Chau,Wu, Ming-Jung
-
p. 2493 - 2499
(2018/04/16)
-
- Palladium catalyzed chloroethoxylation of aromatic and heteroaromatic chlorides: An orthogonal functionalization of a chloroethoxy linker
-
A novel disconnection based on cross-coupling chemistry was designed to access pharmaceutically relevant aryl-aminoethyl ethers. The developed palladium-catalyzed functionalization of aryl- and heteroaryl chlorides with a sodium tetrakis-(2-chloroethoxy) borate salt is orthogonal to the simple nucleophilic replacement of the chloro function of the ethylene linker. The transformation enables efficient 2-chloroethoxylation in the absence of an additional external base. Subsequent amine substitution of the alkyl halide affords 2-aminoethoxy arenes. The applicability of this method was demonstrated through the synthesis of various aryl- and heteroaryl-alkyl ethers, including the intermediates of marketed drug molecules.
- Petho, Bálint,Vangel, Dóra,Csenki, János T.,Zwillinger, Márton,Novák, Zoltán
-
supporting information
p. 4895 - 4899
(2018/07/15)
-
- Sulfoxide compound and method of producing benzothiophene derivatives using the same
-
A sulfoxide compound and method of producing benzothiophene derivatives using the same are provided. The sulfoxide compound is represented by formula (I), wherein R1 and R2 are individually and independently benzoyl group; alkyl, acyl or silyl group of C1-C6 straight chain or branched chain; or alkenyl group of C3-C6 straight chain or branched chain; and X is halogen atom. The sulfoxide compound reacts with alkynyl compound, and then the synthesis efficiency of benzothiophene derivatives can be effectively increased.
- -
-
-
- Piperidine nucleophilic substitution without solvent: An efficient synthesis of raloxifene
-
Mild and high-yielding synthesis is described for raloxifene via piperdine nucleophilic substitution of a new raloxifene intermediate 3-aroyl-2-aryl-substituted benzo[b]thiophenes, which is obtained by acylation of para-substituted benzoyl chlorides and 2-arylbenzo[b]thiophenes. The key step is solvent free and offers valuable advantages, such as low cost, and is suitable for industrial production.
- Yang, Yewei,Zhang, Tao,Huang, Wenhai,Shen, Zhenrong
-
p. 3271 - 3276
(2015/10/06)
-
- A PROCESS FOR PREPARING BENZO[B]THIOPHENE DERIVATIVES
-
The present invention relates in general to the field of organic chemistry, and in particular to the preparation of benzo[b]thiophene derivatives. These benzo[b]thiophene derivatives are useful as intermediates in the synthesis of pharmaceutically active agents such as raloxifene or derivatives thereof.
- -
-
-
- A process for preparing benzo[b]thiophene derivatives
-
The present invention relates in general to the field of organic chemistry, and in particular to the preparation of benzo[b]thiophene derivatives. These benzo[b]thiophene derivatives are useful as intermediates in the synthesis of pharmaceutically active agents such as raloxifene or derivatives thereof.
- -
-
Page/Page column 46
(2011/05/05)
-
- A process for preparing benzo[b]thiophene derivatives
-
The present invention relates in general to the field of organic chemistry, and in particular to the preparation of benzo[b]thiophene derivatives. These benzo[b]thiophene derivatives are useful as intermediates in the synthesis of pharmaceutically active agents such as raloxifene or derivatives thereof.
- -
-
Page/Page column 26
(2011/06/10)
-
- A PROCESS FOR PREPARING BENZO[B]THIOPHENE DERIVATIVES
-
The present invention relates in general to the field of organic chemistry, and in particular to the preparation of benzo[b]thiophene derivatives. These benzo[b]thiophene derivatives are useful as intermediates in the synthesis of pharmaceutically active agents such as raloxifene or derivatives thereof.
- -
-
Page/Page column 38-39
(2011/05/06)
-
- An efficient synthesis of raloxifene in ionic liquid: A Green Approach
-
An efficient and green procedure for the synthesis of raloxifene has been developed by using Suzuki couplings, Friedel-Crafts acylation, and copper catalyzed coupling reactions in an ionic liquid.
- Shinde, Pravin S.,Shinde, Sandip S.,Renge, Atul S.,Patil, Gajanan H.,Rode, Ambadas B.,Pawar, Rajendra R.
-
experimental part
p. 8 - 10
(2010/04/23)
-
- Intermediates and processes for preparing benzo (b) thiophenes
-
The instant invention provides processes for preparing compounds of formula IV, V, and IX, having the structures provided hereinbelow: These compounds are useful intermediates in the further preparation of benzo[b] thiophenes.
- -
-
-
- Synergistic methodologies for the synthesis of 3-aroyl-2- arylbenzo[b]thiophene-based selective estrogen receptor modulators. Two concise syntheses of raloxifene
-
Difunctionalized benzo[b]thiophene intermediates are prepared which allow fully independent elaboration of the 2-aryl position or the tether position of benzo[b]thiophene-based selective estrogen receptor modulators (SERMs). Two concise syntheses of the SERM raloxifene (Evista) are presented.
- Bradley, David A.,Godfrey, Alexander G.,Schmid, Christopher R.
-
p. 5155 - 5159
(2007/10/03)
-
- Nucleophilic aromatic substitution on 3-aroyl-2-arylbenzothiophenes. Rapid access to raloxifene and other selective estrogen receptor modulators
-
Versatile, mild and high yielding methods for nucleophilic aromatic substitution of 2-dialkylamino-1-ethoxides and related nucleophiles on 3- aroyl-2-arylbenzothiophene nuclei are presented. A short synthesis of raloxifene is detailed.
- Schmid, Christopher R.,Sluka, James P.,Duke, Kristin M.
-
p. 675 - 678
(2007/10/03)
-
- Intermediates and processes for preparing benzothiophene compounds
-
The present invention provides a novel process for preparing a compound of formula I STR1 wherein R1 and R2 combine to form C4 -C6 polymethylene, --CH2 CH(CH3)CH2 CH2 --, --CH2 C(CH3)2 CH2 CH2 --, or --CH2 CH2 OCH2 CH2 --; or a pharmaceutically acceptable salt or solvate thereof. Also provided intermediates of formulae II and IV STR2 wherein Z is a leaving group.
- -
-
-
- Antiestrogenic and antiandrugenic benzothiophenes
-
6-Hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, its ethers and esters, and the physiologically acceptable acid addition salts thereof, are valuable antiestrogens and antiendrogens.
- -
-
-
