87833-61-2Relevant articles and documents
Formoterol, pharmaceutically acceptable salt thereof and preparation method of intermediate
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, (2019/04/10)
The invention relates to formoterol, a pharmaceutically acceptable salt thereof and a preparation method of an intermediate. The method for purifying the formoterol intermediate (a compound shown as aformula V) comprises the following steps of: I) perform
Benzylether fumaric acid luck not Trow an important intermediate for the synthesis of compound
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, (2017/01/23)
The invention discloses a synthetic method of a formoterol fumarate important intermediate benzyl ether compound. The synthetic method comprises the following steps: enabling a compound I to react with a compound II in an organic solvent at 100-120 DEG C for 4-6 hours under the concerted catalysis of a catalyst (I) and a catalyst (II); and by using an inorganic alkaline substance as an acid-binding agent in the reaction process, after the reaction ends, adding water to perform cooling and crystallization, and filtering to obtain the benzyl ether compound. The synthetic steps disclosed by the invention perform concerted catalysis on benzyl etherification reaction between a substitute and benzyl chloride by adopting the two catalysts at the same time, and can be used for increasing the reaction speed, shortening the reaction time, shortening the total reaction time to 4 hours from 48 hours, and greatly improving the production efficiency; and after the reaction ends, the qualified benzyl ether compound (of which the content is more than 98%) can be obtained without refining; the synthetic method disclosed by the invention is more suitable for the large-scale industrial production of formoterol fumarate.
Large-scale synthesis of enantio- and diastereomerically pure (R,R)-formoterol
Hett, Robert,Fang, Qun K.,Gao, Yun,Wald, Stephen A.,Senanayake, Chris H.
, p. 96 - 99 (2013/09/08)
(R,R)-Formoterol (1) is a long-acting, very potent β2-agonist, which is used as a bronchodilator in the therapy of asthma and chronic bronchitis. Highly convergent synthesis of enantio- and diastereomerically pure (R,R)-formoterol fumarate is achieved by a chromatography-free process with an overall yield of 44%. Asymmetric catalytic reduction of bromoketone 4 using as catalyst oxazaborolidine derived from (1R, 2S)-1-amino-2-indanol and resolution of chiral amine 3 are the origins of chirality in this process. Further enrichment of enantio- and diastereomeric purity is accomplished by crystallizations of the isolated intermediates throughout the process to give (R,R)-formoterol (1) as the pure stereoisomer (ee, de >99.5%).
