2,6-Di-tert-butyl-4-methylphenol → 4-Ethenyl-2-fluoroaniline

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Reaction Steps

As depicted in above Scheme 20, 2-fluoro-4-iodoaniline is reacted with tertakis(triphenylphosphine)palladium and tributylvinyltin in the presence with catalitically amount of 2,6-di-tert-butyl-4-methylphenol to obtain 2-fluoro-4-vinylaniline (21-1). The resulting compound is reacted with sulfonylating agent such as methane sulfonyl chloride in the presence of pyridine solvent to produce N-(2-fluoro-4-vinylphenyl)methanesulfoneamide (20-2) and oxidized with oxidizing agent e.g., osmium tetroxide and sodium periodate in the presence of acetone-water mixture solvent to aldehyde intermediate (20-3). The aldehyde compound is reacted with Grignard reagent to obtain alcohol intermediate (2-4 to 20-7) and further reacted with DPPA (diphenylphosphorylazide) and DBU (1,8-diazabicyclo[5,4,0]undec-7-ene) in the presence with toluene solvent to produce azide compound (20-8 to 20-11). The azide intermediate is finally reduced with reducing agent such as Pd/C to produce purposed amine derivative (13-11 t 13-13) selectively.

Provenance & Evidence