Synthetic method of (S)-2-benzyloxy propionaldehyde

Abstract

Disclosed is a synthetic method of (S)-2-benzyloxy propionaldehyde. The synthetic method includes the following concrete steps: (1) firstly, (S)-2-benzyloxy propionic acid with an acylation reagent toobtain (S)-2-benzyloxy propionyl chloride; and (2) adding a palladium on barium sulfate catalyst into o-xylene, subjecting the palladium on barium sulfate catalyst and the o-xylene to a reduction reaction for 15-30 minutes, adding the (S)-2-benzyloxy propionyl chloride prepared in the step (1), continuing to heat for reflux reaction in a hydrogen atmosphere until the reaction mixture does not absorb hydrogen, filtering off the catalyst after the reaction is completed, and removing the o-xylene to obtain the product (S)-2-benzyloxy propionaldehyde. Instead of using diisobutylaluminium hydride,which is prone to ignition after treatment, as a reaction raw material, the acylation reagent which is low in cost, safer and more environmentally friendly and the palladium on barium sulfate catalyst which can be recycled for many times are used as reaction raw materials, the reaction process is more consistent with the principle of atomic economy, and the reaction is more mild.

Description

technical field [0001] The invention relates to the technical field of synthesis of posaconazole intermediates, and specifically designs a synthesis method of (S)-2-benzyloxypropanal. Background technique [0002] Posaconazole (chemical name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-tri Azol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3 -base]-1,2,4-triazole-3-ketone, English name: Posaconazole), the structural formula is as follows: [0003] [0004] Developed by the Schering-Plough Company of the United States and approved by the FDA in September 2006, it is a broad-spectrum triazole antifungal drug with high lipophilicity. The trade name is Noxafil (Nuo Kefei), oral suspension, mainly used to prevent invasive aspergillus and candida infections in patients aged thirteen and over, and to treat oropharyngeal candida infections and resistance to fluconazole and voriconazole Medicine for oropharyngeal candida infect...

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Problems solved by technology

[0009] This method will use expensive, easy to catch fire during aftertreatment, solid waste is more, the big diisobutyl aluminum hydride of pollution is used as reaction raw material, and this can cause the production danger of (S)-2-benzyloxy propionaldehyde Large, the production cost is greatly increased, which is not conducive to large-scale industrial production

[0010] The patent application document with application number CN201711474238.8 discloses the synthesis method of (S)-2-benzyloxypropanal as shown below. Although this method avoids the use of diisobutyl aluminum hydride, the entire reaction route is atom-economical. Not high, the use and aftertreatment of ethylenediamine will also cause certain environmental pressure:

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