Continuous Platform to Generate Nitroalkanes On-Demand (in situ) using Peracetic Acid-Mediated Oxidation in a PFA Pipes-in-Series Reactor.

Autor:	Tsukanov SV; Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, Indiana 46285, Unites States.; Department of Chemistry and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37235, United States., Johnson MD; Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, Indiana 46285, Unites States., May SA; Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, Indiana 46285, Unites States., Kolis SP; Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, Indiana 46285, Unites States., Yates MH; Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, Indiana 46285, Unites States., Johnston JN; Department of Chemistry and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37235, United States.
Jazyk:	angličtina
Zdroj:	Organic process research & development [Org Process Res Dev] 2018 Aug 17; Vol. 22 (8), pp. 971-977. Date of Electronic Publication: 2018 Jul 19.
DOI:	10.1021/acs.oprd.8b00113
Abstrakt:	The synthetic utility of the aza-Henry reaction can be diminished on scale by potential hazards associated with the use of peracid to prepare nitroalkane substrates, and the nitroalkanes themselves. In response, a continuous and scalable chemistry platform to prepare aliphatic nitroalkanes on-demand is reported, using the oxidation of oximes with peracetic acid and direct reaction of the nitroalkane intermediate in an aza-Henry reaction. A uniquely designed pipes-in-series plug flow tube reactor addresses a range of process challenges including stability and safe handling of peroxides and nitroalkanes. The subsequent continuous extraction generates a solution of purified nitroalkane which can be directly used in the following enantioselective aza-Henry chemistry to furnish valuable chiral diamine precursors in high selectivity, thus, completely avoiding isolation of potentially unsafe low molecular weight nitroalkane intermediate. A continuous campaign (16 h) established that these conditions were effective in processing 100 g of the oxime and furnishing 1.4 L of nitroalkane solution. Competing Interests: Notes The authors declare no competing financial interest.
Databáze:	MEDLINE
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