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40.1.1.5.4.5.1.5 Method 5: Cleavage of the C—N Bond Using Solid-Supported Reagents

DOI: 10.1055/sos-SD-140-00180

Scammells, P. J.Science of Synthesis Knowledge Updates, (20132438.

Tertiary N-methylamines can be efficiently N-demethylated using a solid-supported de­oxygenation system that employs a chromatography-like setup.[‌28‌] In this approach, the amine is charged onto a preparative chromatographic column loaded with different solid reagents in three reaction zones. In the first zone, the N-methylamine is oxidized to the corresponding N-oxide with sodium percarbonate. In the second zone, N-demethylation is effected using the sodium salt 13 of 4,6-dichloro-1,3,5-triazin-2-ol. Finally, in the third zone, purification of the desired secondary amine is achieved by removal of formed formaldehyde by absorption onto a 1:1 mixture of neutral and basic alumina. An example of this process is given in Scheme 7, where 4-methylmorpholine undergoes N-demethyl­ation via formation of the N-oxide to give morpholine as the hydrochloride salt 14 after acidic workup.

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References


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