ORGN 141 |
| Barluenga et al. reported highly stereoselective reduction of 3-N,N-dibenzylamino-1-chloromethyl-4-phenylbutan-2-one 2 with NaBH4 to give the corresponding RS-aminoalcohol. Applying this technology, we have developed a process for the synthesis of RS-3-N-tert-butoxycarbonylamino-1,2-epoxy-4-phenylbutane 5. Thus, N,N-dibenzyl group was deprotected by hydrogenolysis and protected by Boc group to give RS-3-N-tert-butoxycarbonylamino–1-chloromethyl-4-phenylbutan-2-ol 4, which is easily converted into the desired product using a base. Though the process seems to be promising route, the problem is how to remove impurities without chromatography. We have established very unique and practical method to remove these impurities without chloromatography and proof that the process is scalable. One of the major impurities is bischloromethylated compound 3, and the other one is SS- isomer. The former impurity can be removed by a selective protection and the latter one can be done by a selective crystallization. The demonstration of this process on large scale (>100 kg) will also be described.
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Asymmetric Reactions and Syntheses, Physical Organic Chemistry, Combinatorial Chemistry, Total Synthesis
8:00 PM-10:00 PM, Sunday, 26 March 2006 Georgia World Congress Center -- Ex. Hall B4, Poster
Division of Organic Chemistry |
