Quinolines, fluoro-, syntheses

Catalytic synthesis of l-ethyl>6-fluoro-l,4-dihydro-4-oxo-7-(l-piperazinyl)-quinoline-3-carboxylic acid ethyl ester (Norfloxacin ethyl ester) (15a). To a dry 15 mL recovery flask equipped with a reflux condenser was added 13 (150 mg, 0.5 mmole), (R)-binap (10 mg, 0.017 mmole), cesium carbonate (360 mg, 0.950 mmole), piperazine (215 mg, 2.5 mmole), Pd2(dba)3 (10 mg, 0.010 mmole), and 1.5 mL of DMF. The reaction vessel was purged with nitrogen and heated to reflux. After three hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. The residue was purified by thin-layer chromatography on a 500 micron silica gel preparative plate with an elution mixture of chloroform methanol water ammonia (80 20 2 0.2) to give 101 mg of 15a as an off-white solid in 58% yield and, separately, 29 mg of 17 as a light brown solid in 22% yield. Using this procedure, the yield of 15a... 

Catalytic synthesis of l-ethyl-6-fluoro-l,4-dihydro-4-oxo-7-(l-methyl-piperazinyl)-quinoline-3-carboxylic acid ethyl ester (15b). To a dry 15 mL... 

Stereoselective multi-steps synthesis of fluorinated 2,3-dihydroquinolin (lH)-ones proceeding as a one-pot transformation has been described [50]. The Ts-protected 0-(2-anilino)- 0-ketoesters 75 are capable of reacting with a variety of aldehydes under mild conditions to form fluorinated quinolines 76 in good yields (up to 98 %) and high diastereo selectivities (dr up to 99 1) (Scheme 30). The compounds 76 are considered as versatile synthetic intermediates, and, indeed, they can be transformed into functionalized heterocyclic derivatives. For example, decarboxylation of compounds 76 results in the formation of 3-fluoroquinolines 77, while reduction with NaBH4 affords a-fluoro-)3-hydroxy esters 78. 

Wada Y, Mori T, Ichikawa J (2003) A facile synthesis of 2,3-disubstituted 3-fluoro-quinolines via intramolecular cyclization of o-cyanomethylamino-p, P-difluorostyrenes. Chem Lett 32 1000-1001... 

Hosokawa T, Matsumura A, Katagiri T, Uneyama K (2008) One-pot synthesis of 3-fluoro-4-(trifluoromethyl)quinolines from pentafluoropropen-2-ol and their molecular modification. J Org Chem 73 1468-1474... 

Stadlwieser J, Barbler P, Taylor S (1998) 8-Fluoro-6-(methoxymethoxy)-quinoline synthesis and regioselective functionalization via reaction with organolithium compounds. Helv Chim Acta 81 1088-1094... 

Bennacef I, Tymdu S, DhiUy M, Lasne M, Debrayne D, Perrio C, Barre L (2004) Synthesis and biological evaluation of novel fluoro and iodo quinoline carboxamides as potential ligands of NK-3 receptors for in vivo imaging studies. Biootg Med Chem 12 4533 541... 

Edmont D, Chenault J (2003) 8-Fluoro-4-hydroxy-l//-[l,2,4]triazino[4,5-a]-quinoline-l,6(2//)"dion - synthesis and reactivity. J Heterocycl Chem 40 789-793... 

Segawa J, Kazuno K, Matsuoka M, Amimoto I, Ozaki M, Matsuda M, Tomii Y, Kitano M, Kise M (1995) Studies on pyridonecarboxyUc acids. IV. Synthesis and antibacterial activity evaluation of S-(-)- and R-(+)-6-fluoro-l-methyl-4-oxo-7-(l-piperazinyl)-4H-[l,3]thia-zeto-[3,2-a]quinoline-3-carboxylic adds. Chem Pharm BuU 43 1238-1240... 

Sharma K, Fernandes P (2006) Synthesis and biological activity of substituted quinolones derived from 6-fluoro-3-carbethoxy-lH-quinolin-4-one. Ind J Heterocycl Chem 15 253-258... 

For the synthesis of functionalized fluoroisoquinolines, cycUzation of lV-[2-(fluorophenyl)ethyl]amides followed by aromatization was effective, which is called the Bischler-Napieralski reaction and is a typical method for 1-substituted 3,4-dihydroisoquinoUnes directed toward isoquinoline synthesis [20]. The reaction smoothly proceeded, irrespective of the positions of fluorine, when lV-[2-(fluorophenyl)ethyl]-2-phenylacetamides were used (Scheme 6) [11]. Notably, 8-fluoro-3,4-dihydroisoquinoline was not obtained by this method because Al-[2-(3-fluorophenyl)ethyl]-2-phenylacetamides gave 6-fluoro-3,4-dihydroiso-quinolines exclusively. The reduction of 3,4-dihydroisoquinolines to... 

---