The synthesis of 3‐bromo‐2,4,5‐trifluorobenzoic acid and its conversion to 8‐bromoquinolonecarboxylic acids

Abstract

A series of 8‐bromo‐4‐oxo‐3‐quinolinecarboxylic acids was prepared via the borate ester, 8. The key intermediate in the synthesis of the final products 10a‐10d was 3‐bromo‐2,4,5‐trifluorobenzoic acid (3), conveniently prepared in two steps from the known oxazoline, 1. The preparation of 10a‐10d is a significant improvement of the literature procedure currently available for the synthesis of these compounds.

A Novel Antibacterial 8-Chloroquinolone with a Distorted Orientation of the N1-(5-Amino-2,4-difluorophenyl) Group

“…Previously, an analogous nucleophilic substitution of an 8-Br quinolone derivative without decarboxylation by derivatizing to its boron difluoride intermediate was accomplished. 19 Applying this method to the reaction of 13d,e with 3-aminoazetidine did not improve the yield. After the examination of many additives (organic bases and inorganic salts) and reaction conditions (temperature and solvent), Li + ion was identified as a novel accelerator for the C-7 substitution reaction.…”

“…Such conditions resulted in low yields (<20%) because of the competitive decarboxylation at the 3-position. Previously, an analogous nucleophilic substitution of an 8-Br quinolone derivative without decarboxylation by derivatizing to its boron difluoride intermediate was accomplished . Applying this method to the reaction of 13d , e with 3-aminoazetidine did not improve the yield.…”

An efficient and scalable synthesis of (2R,αS)‐3,4‐dihydro‐2‐[3‐(1,1,2,2‐tetrafluoroethoxy)phenyl]‐5‐[3‐(trifluoromethoxy)phenyl]‐α‐(trifluoromethyl)‐1(2H)‐quinolineethanol: A potent CETP inhibitor

“…The organic layer was dried, concentrated, and purified by flash column chromatography (10-20% EtOAc in hexane) to provide 114 mg (86%) of 13 as an oil. 1 (14). To a solution of 13 (220 mg, 0.413 mmol) and CH 2 Cl 2 (3 mL) was added methanesulfonyl chloride (0.040 mL, 0.52 mmol) and Et 3 N (0.086 mL, 0.62 mmol).…”

“…In a solvent-free system, bromination [13] of 4 (26 g) with N-bromosuccimide and AIBN at 90 C for 5 h gave benzyl bromide 5 in 95% yield. The b-keto ester 7 was synthesized by acylation of ethyl hydrogen malonate with 3-tetrafluoroethoxybenzoyl chloride, followed by decarboxylation during acidic work-up procedure [14]. The product was a mixture of b-keto ester 7a and its tautomer enol 7b in $3:1 ratio.…”