Development of a Practical and Scalable Synthesis of (R)- and (S)-3-Amino-2-[(benzyloxy)methyl]propan-1-ol Monohydrochloride: A Useful C-4 Chiral Building Block

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• 作者：Shinya Yoshida ; Kazuyoshi Obitsu ; Yasumasa Hayashi ; Mitsuyoshi Shibazaki ; Takenori Kimura ; Takumi Takahashi ; Toru Asano ; Hirokazu Kubota ; Takashi Mukuta
• 刊名：Organic Process Research & Development
• 出版年：2012
• 出版时间：September 21, 2012
• 年：2012
• 卷：16
• 期：9
• 页码：1527-1537
• 全文大小：422K
• 年卷期：v.16,no.9(September 21, 2012)
• ISSN：1520-586X

文摘

The development of a practical and scalable synthesis of a C-4 chiral amine building block (R)-1路HCl and (S)-1路HCl is described. This important chiral intermediate (R)-1路HCl is efficiently synthesized from the commercially available, inexpensive, and simple 2-(hydroxymethyl)-1,3-propanediol (31) using lipase-catalyzed enantioselective hydrolysis as a key reaction. Development resulted in a telescoped process that was operated successfully and reproducibly in a pilot-plant-scale synthesis, and 22 kg of chiral amine (R)-1路HCl was prepared in the first scale-up synthesis. This synthetic method is also useful for preparation of the important chiral building block (S)-1路HCl, which is the enantiomer of (R)-1路HCl.