Practical Diastereoselective Synthesis and Scale-up Study of (+)-2-((1R,2R,3R,5S)-2-Amino-6,6-dimethylbicyclo[3.1.1]hept-3-yl)ethanol: A Key Intermediate of the Novel Prost

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• 作者：Takemasa Hida ; Susumu Mitsumori ; Tsunetoshi Honma ; Yoshiharu Hiramatsu ; Hiroshi Hashizume ; Tetsuo Okada ; Makoto Kakinuma ; Kyozo Kawata ; Katsuo Oda ; Aiko Hasegawa ; Toshiaki Masui ; Hideo Nogusa
• 刊名：Organic Process Research & Development
• 出版年：2009
• 出版时间：November 20, 2009
• 年：2009
• 卷：13
• 期：6
• 页码：1413-1418
• 全文大小：232K
• 年卷期：v.13,no.6(November 20, 2009)
• ISSN：1520-586X

文摘

A new synthetic process was developed for (+)-2-((1R,2R,3R,5S)-2-amino-6,6-dimethylbicyclo[3.1.1]hept-3-yl)ethanol, a key intermediate of S-5751. Diastereoselective alkylation of (+)-nopinone with ethyl bromoacetate, formation of O-methyl oxime, and diastereoselective reduction with NaBH₄−AlCl₃ could be safely carried out. Stereochemistry of the (1R,2R,3R,5S)-6,6-dimethylbicyclo[3.1.1]heptane ring was discussed to achieve high diastereoselectivity on these reactions. For the scale-up, detailed consideration was given to the safety of the NaBH₄−AlCl₃ reduction.