Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:12])[CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2.CN1[CH2:18][CH2:17][CH2:16][C:15]1=O.C([Mg]Cl)CCC>O1CCCC1>[CH2:15]([C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:12])[CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2)[CH2:16][CH2:17][CH3:18]
Reactant: Fc1cc(Cl)cc2cccnc12
Reactant: CN1CCCC1=O
Agent: CCCC[Mg]Cl
Solvent: C1CCOC1
Product: CCCCc1cc(F)c2ncccc2c1
Temperature: -5 °C
Reaction time: 0.25 h
Yield: 82.5 %

Procedure:
Under nitrogen, 6-chloro-8-fluoroquinoline (for example, as prepared for Intermediate 5) (4.6 kg, 1.0 eqv) was added to N-methylpyrrolidinone (46 L, 10 vol). To this mixture, ferric acetylacetonate (0.89 kg, 0.1 eqv) was added and the reaction mass cooled to 0 to −10° C. A solution of n-butyl magnesium chloride (commercially available, for example, from Aldrich) (14.84 L, 1.35 eqv of 2.3M grignard in tetrahydrofuran) was added slowly over approximately 4 hours at between 0 to −10° C. and the reaction was stirred for 10 to 20 min. The progress of the reaction was monitored by HPLC. As there was more than 2% starting material a further portion of n-butyl magnesium chloride was added (0.52 L, 0.05 eqv of 2.3M grignard in tetrahydrofuran) at 0 to −10° C. over 10 to 30 min. After passing the HPLC (starting material not more than 2%), the reaction mixture was quenched with ammonium chloride solution (4.6 kg, 1 wt, in 101 L water) keeping the temperature below 35° C., an the reaction mixture was stirred at approximately 27° C. for 15-30 min. A dilute solution of aqueous HCl (3.5 vol, 14.6 L [made up as bulk solution of 4.6 L 35% HCl in 13.8 L water]) was then added into the reaction mixture until pH 1-2 was reached. The reaction mass was extracted at pH 1 to 2 with ethyl acetate (46 L, then 28 L×3). The combined organic layers were then washed with water (69 L, 15 vol) and dilute ammonia solution (46 L [41.4 L water and 4.6 L 22.38% aqueous ammonia solution). The organic layer was washed with water (55.2 L×3), the organic layer was separated and concentrated in vacuo (vacuum no less than 600 mm Hg), keeping the temperature below 70° C. Toluene (4.6 L, 1 vol) was then added and the mixture concentrated in vacuo (vacuum no less than 600 mm Hg), keeping the temperature below 70° C. to a crude oil to remove traces of ethyl acetate. The residue was diluted in toluene (6.9 L, 1.5 vol) and added to n-hexane (138 L, 30 vol) with stirring at 25-35° C. After 1 to 2 hr, the mass was filtered through celite (4.6 kg) and the celite bed was washed with mixture of toluene and hexane (1:10, 0.92 L, 0.2 vol toluene and 9.2 L, 2 vol hexane) followed by hexane washing (46 L, 10 vol). The combined filtrate was stirred with silica gel (6.9 kg, 1.5 wt) for 1.5 to 2.5 hr at 25-35° C. Silica gel was filtered off and filtered silica gel was washed with a mixture of hexane and triethylamine (20:1 mixture, 5×48.3 L). The combined filtrate was then concentrated twice in vacuo (vacuum not less than 600 mm Hg) keeping the temperature below 70° C. Toulene (4.6 L, 1 vol) was then added to the residue (approximately 10 L) and again concentrated in vacuo (vacuum not less than 650 mm Hg) keeping the temperature below 70° C. to remove traces of solvent (toluene less than 10%). The residue was cooled, unloaded and stored under nitrogen. The title compound was obtained in 82.5% yield (4.25 kg) and in 99.0% purity.