67499-71-2Relevant academic research and scientific papers
Preparation method of clomastine fumarate with high chiral purity
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, (2020/07/15)
The invention discloses a preparation method of chlormastine fumarate with high chiral purity. The preparation method comprises the following five steps: step 1, taking D-arginine as a resolving agentto resolve a compound N-methyl-2-(2-hydroxyethyl) pyrrolidine shown in a formula 2 to obtain a compound shown in a formula 3; step 2, reacting the compound shown in the formula 3 with thionyl chloride for chlorination to obtain a compound shown in a formula 4; step 3, reacting the compound shown in the formula 4 with a compound 1-((4-chlorphenyl)-1-phenyl) ethanol shown in a formula 5 under the condition that sodium amide is strong base to obtain a compound shown in a formula 6; step 4, resolving the compound shown in the formula 6 by adopting tartaric acid to remove chiral isomer impurities,and obtaining a compound shown in a formula 7 at the same time; and step 5, salifying the compound shown in the formula 7 and fumaric acid to obtain a compound chlormastine fumarate shown in a formula 1. The prepared clomastine fumarate bulk drug has high chiral purity, the product quality meets the injection drug requirements specified in pharmacopeia, the technological process is simple and easy to control, the operability is high, and industrial production can be achieved.
Asymmetric synthesis of H1 receptor antagonist (R,R)-clemastine
Lee, Sun Young,Jung, Jung Wha,Kim, Tae-Hyun,Kim, Hee-Doo
, p. 2131 - 2136 (2015/12/08)
The first asymmetric synthesis of (R,R)-clemastine (1) has been accomplished by the coupling of (R)-tertiary alcohol 2 and (R)-chloroethylpyrrolidine 3 via O-alkylation. (R)-Tertiary alcohol 2 was synthesized by stereoselective alkylation of chiral α-benz
Synthesis of (-)-(S, S)-clemastine by invertive N → C aryl migration in a lithiated carbamate
Fournier, Anne M.,Brown, Robert A.,Farnaby, William,Miyatake-Ondozabal, Hideki,Clayden, Jonathan
supporting information; experimental part, p. 2222 - 2225 (2010/08/04)
The first enantioselective synthesis of the antihistamine agent clemastine, as its (S,S)-stereoisomer, has been achieved by ether formation between a proline-derived chloroethylpyrrolidine and an enantiomerically enriched tertiary alcohol. The tertiary alcohol was formed from the carbamate derivative of α-methyl-p-chlorobenzyl alcohol by invertive aryl migration on lithiation. The (S,S)-stereochemistry of the product confirms the invertive nature of the rearrangement.
SUBSTITUTED BENZHYDRYLETHERS
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Page/Page column 34, (2009/08/18)
Disclosed herein are substituted benzhydrylethers of Formula I, processes of preparation thereof, pharmaceutical compositions thereof, and methods of their use thereof.
