Alcohols azide-based amine conversions

With a common intermediate from the Medicinal Chemistry synthesis now in hand in enantiomerically upgraded form, optimization of the conversion to the amine was addressed, with particular emphasis on safety evaluation of the azide displacement step (Scheme 9.7). Hence, alcohol 6 was reacted with methanesul-fonyl chloride in the presence of triethylamine to afford a 95% yield of the desired mesylate as an oil. Displacement of the mesylate using sodium azide in DMF afforded azide 7 in around 85% assay yield. However, a major by-product of the reaction was found to be alkene 17, formed from an elimination pathway with concomitant formation of the hazardous hydrazoic acid. To evaluate this potential safety hazard for process scale-up, online FTIR was used to monitor the presence of hydrazoic acid in the head-space, confirming that this was indeed formed during the reaction [7]. It was also observed that the amount of hydrazoic acid in the headspace could be completely suppressed by the addition of an organic base such as diisopropylethylamine to the reaction, with the use of inorganic bases such as... 

Funk s synthesis in 2004 [28] of perophoramidine (Scheme 3), commenced with a base-catalyzed coupling reactiOTi between indole 19 and 3-bromoindolin-2-one 20. Boc protectiOTi of the resulting lactam 21 followed by reduction of the azido functionality led to transamidation and closure of the resulting carbamate upon the indolenine to deliver the aminal 22. Chemoselective chlorination and protection of the lactam followed by a two-step deprotection and conversion of the resulting alcohol to the azide afforded amide 23. A second transamidation reaction followed by selective methylation gave lactam 24. Treatment of lactam 24 with Meerwein s reagent gave imidate 25, which imderwent a Fukuyama deprotection of the sulfur... 

A method for nucleophilic aromatic substitution by carbanions is based on the coordination of a chromium tricarbonyl unit with an aromatic ring, which increases its reactivity the unit can be easily attached and removed. Amines can be efficiently phenylated with tri-carbonylcyclohexadienone iron . N,N-Methylphenylaminotriphenyl-phosphonium iodide is an efficient reagent for the conversion of alcohols into sec. and tert. amines or into azides... 

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