Stage #1: 5-fluoro-8-methylquinoline With chromium(VI) oxide; sulfuric acid In water at 90 - 105℃;
Stage #2: With sodium hydroxide In dichloromethane; water
Step 2: S-fluoroquinoline-S-carboxylic acidA solution (0.15 M) of 5-fluoro-8-methylquinoline (from Step 1) in sulphuric acid/water (8/5, v/v) was heated at 900C and treated portionwise with Cr?3 (10 eq.) at such a rate to maintain the temperature below 1050C. After cooling the reaction mixture to 00C, CH2Cl2 and water were carefully added. Then, NaOH was added until pH = 5. The organic layer was separated and dried. Evaporation of the solvent afforded (25%) the title compound as a pale brown solid; MS (ES+) m/z 192 (M+H)+.
With chromium(VI) oxide; sulfuric acid In water at 90 - 100℃; Inert atmosphere;
With platinum(IV) oxide; hydrogen; acetic acid for 3h;
With hydrogen In acetic acid for 3h; Atmospheric pressure;
Step 3: 5-fluoro-l,2,3,4-tetrahvdroquinoline-8-carboxylic acid A solution (0.25 M) of 5-fluoroquinoline-8-carboxylic acid (from Step 2) in acetic acid was treated with PtO2 (0.3 eq.) and stirred under hydrogen at atmospheric pressure for 3 h. The catalyst was filtered off and the solution was concentrated to dryness under reduced pressure to afford a residue, which was redissolved with DMSO and purified by RP-HPLC (Conditions: Waters X-TERRA Cl 8, 5 micron, 19 x 100 mm; flow: 20 mL/min; Gradient: A: H2O + 0.1% TFA; B: MeCN + 0.1% TFA; 80% A isocratic for 1 min, linear to 20% A in 9 min) affording (40%) the title compound as a white solid; MS (ES+) m/z 196 (M+H)+.