Reaction SMILES: C([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)(OC(C)(C)C)=O.CC(C)([O-])C.[Na+].[CH2:21]([C:25]1[CH:26]=[C:27]2[C:32](=[C:33](F)[CH:34]=1)[N:31]=[CH:30][CH:29]=[CH:28]2)[CH2:22][CH2:23][CH3:24].[Na].C(N1CCC(O)CC1)(OC(C)(C)C)=O.[Cl-].[NH4+].Cl.C(O)(C)C>CN1CCCC1=O.CN(C=O)C.O.C(O)(=O)C.C(OCC)(=O)C>[CH2:21]([C:25]1[CH:26]=[C:27]2[C:32](=[C:33]([O:14][CH:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)[CH:34]=1)[N:31]=[CH:30][CH:29]=[CH:28]2)[CH2:22][CH2:23][CH3:24]
Reactant: CC(C)(C)OC(=O)N1CCC(O)CC1
Reactant: CCCCc1cc(F)c2ncccc2c1
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [Cl-]
Solvent: CCOC(C)=O
Solvent: CC(C)O
Solvent: CN(C)C=O
Product: CCCCc1cc(OC2CCNCC2)c2ncccc2c1
Temperature: 25 °C
Yield: 34.24 %

Procedure:
Under a nitrogen atmosphere, N-Boc-4-hydroxypiperidine (commercially available, for example, from Aldrich) (11.66 kg, 1.5 eqv) and sodium tert-butoxide (5.5 kg, 1.5 eqv) was charged into a reactor containing N-methylpyrrolidinone (39.25 L, 5 vol) and stirred at approximately 25° C. to obtain a clear solution. In another reactor under a nitrogen atmosphere was charged 6-butyl-8-fluoroquinoline (for example, as obtained from Stage 1) (7.85 kg, 1.0 eqv) and N-methylpyrrolidinone (31.4 L, 4 vol) under nitrogen and heated to approximately 110° C. over 1-3 hr. From the first reactor, the solution of N-Boc-4-hydroxypiperidine sodium salt in N-methylpyrrolidinone was added slowly over 2-3 hr into the second reactor containing 6-butyl-8-fluoroquinoline in N-methylpyrrolidinone at approximately 110° C. The reaction mixture was stirred for approximately 1 hr at approximately 110° C. and progress of the reaction was monitored by HPLC (starting material not more than 2%). After completion of reaction, the temperature was adjusted to 30-40° C. and a saturated solution of ammonium chloride (7.85 kg ammonium chloride in 157 L water, 20 vol) was added into the reaction mass below 40° C. To this reaction mixture, ethyl acetate (78.5 L, 10 vol) was added followed by acetic acid (1.15 L, 0.15 vol) and stirred well. The organic layer was separated, and aqueous layer was again extracted with ethyl acetate (39.25 L, 5 vol). The combined organics were then washed with water (78.5 L, 10 vol×3). The combined organics were concentrated in vacuo (vacuum not less than 600 mm Hg), keeping the temperature below 60° C. To the concentrated reaction mass, toluene (23.55 L, 3 vol) was added, and the reaction mixture concentrated in vacuo (vacuum not less than 600 mm Hg), keeping the temperature below 60° C. To this crude mass again fresh toluene (78.5 L, 10 vol) was added, followed by 22.8% HCl in iso-propyl alcohol (24.51 L, 3.36 eqv), and reaction mixture was stirred at 70-80° C. for 1-2 hr. The progress of the reaction was monitored by HPLC (starting material less than 2% by HPLC). After completion of reaction, the reaction was cooled to 30-40° C. and water (78.5 L, 10 vol) was added portionwise into the reaction mixture, stirred well and the layers separated. The aqueous layer was washed three times with dichloromethane (78.5 L, 10 vol, then 54.95 L, 7 vol, then 39.25 L, 5 vol). The aqueous layer was slowly basified with sodium hydroxide solution (7.85 kg in 54.95 L water) until pH was 12.5 to 13.5. The product was extracted in dichloromethane (78.5 L, 10 vol, then 39.25 L, 5 vol, ×2). The combined dichloromethane layers were washed with aqueous sodium chloride solution (7.85 kg in 78.5 L water, ×3). The combined organics were concentrated in vacuo (vacuum no less than 600 mm Hg) keeping the temperature below 50° C. In order to remove traces if dichloromethane, N,N′-dimethylformamide (23.6 L, 3 vol) was added and the reaction mass was held at a vacuum of no less than 650 mm Hg, keeping the temperature below 50° C. The title compound (3.76 kg, 34.24% yield) was obtained as solution in N,N′-dimethylformamide and stored at approximately 5° C.