Method for synthesizing precursor of vilanterol intermediate

Abstract

The invention relates to a method for synthesizing (1R)-1-(2, 2-dimethyl-4H-1, 3-benzodioxin-6-yl)-2-nitroethanol, and the route of the method is as follows: the (1R)-1-(2, 2-dimethyl-4H-1, 3-benzodioxin-6-yl)-2-nitroethanol synthesized by adopting the synthesis method is applied to preparation of (5R)-5-(2, 2-dimethyl-4H-1, 3-benzodioxin-6-yl)-1, 2, 4-triazole-3-yl)-2-nitroethanol, and the (1R)-1-(2, 2-dimethyl-4H-1, 3-benzodioxin-6-yl)-2-nitroethanol is used as a raw material. The method can be used for preparing 2, 3-oxazolidine-2-ketone, reaction steps can be shortened, and the method has the advantages of being high in reaction conversion number, high in atom economy, suitable for industrial production and the like. Compared with the currently reported asymmetric Henry reaction synthesis route, the method has the advantages that the price of the catalyst required by the synthesis route is low, the molar yield of the alpha-nitroketone reduction step is greater than 85%, and the method has the characteristics of high asymmetric selectivity and easiness in production.

Description

technical field [0001] The invention belongs to the field of organic chemical synthesis, and in particular relates to a method for synthesizing a precursor of a synthetic vilanterol intermediate, namely (1R)-1-(2,2-dimethyl-4H-1,3- Benzodioxin-6-yl)-2-nitroethanol method. Background technique [0002] (1R)-1-(2,2-Dimethyl-4H-1,3-benzodioxin-6-yl)-2-nitroethanol can be used to synthesize (5R)-5-(2, The precursor of 2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one, while (5R)-5-(2,2- Dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one is an important intermediate in the synthesis of vilanterol, which can be used as a long-acting β2 Adrenergic receptor agonist. [0003] [0004] (1R)-1-(2,2-Dimethyl-4H-1,3-benzodioxin-6-yl)-2-nitroethanol [0005] [0006] (5R)-5-(2,2-Dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one [0007] At present, the current synthetic route of (5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one is as follows Sh...

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Problems solved by technology

[0009] There are many deficiencies in this route: for example, 1) when ketone is carried out chiral catalytic reduction into alcohol in the second step, the chiral catalyst (R)-2-methyl-CBS-oxocatalyst (R)-2-methyl-CBS-oxo oxazoboridine; 2) the route contains two steps of protecting groups and deprotecting groups (respectively triethylsilyl and benzyl), and the atom economy is low; 3) the synthetic route steps are longer, including 7 steps

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