Preparation method of formoterol key intermediate

Abstract

The invention provides a preparation method of a formoterol key intermediate (R)-N-(2-(benzyloxy)-5-(2-bromo-1-hydroxyethyl)phenyl)formamide represented by a formula I, wherein asymmetric reduction isperformed by using 1-(4-(benzyloxy)-3-nitrophenyl)-2-bromoethanone (II) as a raw material and using (3aS-cis)-(-)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazole-2-isopropylborane (IV) as a catalyst toobtain a chiral alcohol intermediate (R)-1-(4-(benzyloxy)-3-nitrophenyl)-2-bromoethanol (III) with high enantioselectivity, and then nitro reduction and formylation one-pot reaction are performed to obtain a target product represented by the formula I. Compared with the traditional resolution method, the method of the invention has advantages of high chiral purity of the product, short productionperiod, easy operation, mild condition, convenient post-treatment and high yield, and is suitable for large-scale industrial production.

Description

technical field

[0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a preparation method of a formoterol key intermediate as shown in formula I. Background technique

[0002] (R)-N-(2-(benzyloxy)-5-(2-bromo-1-hydroxyethyl)phenyl)carboxamide has the structure of formula (I):

[0003]

[0004] Hereinafter all are referred to as compounds of formula (I). The compound of formula (I) is a key intermediate in the synthesis of Formoterolfumarate.

[0005] Formoterol fumarate is a β2 sympathomimetic drug, which has the typical basic structure of all sympathomimetic drugs and is a derivative of epinephrine. It binds to the β2 adrenergic receptors in the airway, excites the β2 receptors to relax the tracheal smooth muscle, and achieves the effect of dilating the trachea, thereby relieving symptoms such as wheezing. Formoterol is a drug developed by Japan's Astellas Company for the treatment of asthma and chronic obstructive pulmonary di...

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