Tamim F. Braish

The tandem Michael-SN2 reaction for the construction of the 3-azabicyclo[3.1.0]hexane ring system

Abstract The 3-azabicyclo[3.1.0]-hexane ring system was constructed in a convergent one-pot procedure starting from readily available starting materials, using the intramolecular tandem Michael-SN2 reaction. The methodology was also extended to the synthesis of 3-azabicyclo[4.1.0]heptane ring system.

Synthesis of trovafloxacin using various (1α,5α,6α)-3-azabicyclo[3.1.0]hexane derivatives

Trovafloxacin, a novel broad spectrum antibacterial, contains the unusual (1α,5α,6α)-3-azabicyclo[3.1.0]hexane ring system. The prototype of the industrial synthesis of this ring system and possible mechanistic pathways to exclusive formation of the exo or 6α-nitro derivative 4 are described, which leads to the key 6α-nitro-3-azabicyclo[3.1.0]hexane intermediate 10. The synthesis of 6α-amino-3-azabicyclo[3.1.0]hexane 16 and useful protected exo 6-amino derivatives 15 and 17 follows from 10. These can be coupled with the 7-chloronaphthyridone 18 to yield protected trovafloxacin compounds 20–22 in good yield. The ethyl ester of trovafloxacin 21 can also be accessed from the product of coupling 19, derived from 18 and the exo 6-nitro-3-azabicyclo[3.1.0]hexane compound 12. Removal of protecting groups from 20–22 with methanesulfonic acid yields trovafloxacin mesylate from which trovafloxacin zwitterion 1 can be liberated with base treatment. Zwitterion 1 can also be prepared directly from 16 tosylate salt and naphthyridone-2-carboxylic acid 26.

Synthesis of 2-Bromo-4, 5-Difluorobenzolc Acid

Abstract The synthesis of 2-bromo-4, 5-difluorobenzoic acid was achieved from difluorophthalic anhydride by either using a Losen rearrangement or the Barton bromodecarboxylation reaction.

Formation and Use of Boron Sulfonates

Abstract Boric acid reacts swiftly with p-toluenesulfonyl chloride idine-d 5 to form the unstable boron sulfonate which is observed IR. The utility of this reaction is discussed.