Reaction SMILES: C(N(CC)CC)C.[C:8]([C:10]1[C:11](F)=[C:12]([F:30])[CH:13]=[C:14]2[C:19]=1[N:18]([C@@H:20]1[CH2:22][C@@H:21]1[F:23])[CH:17]=[C:16]([C:24]([O:26]CC)=[O:25])[C:15]2=[O:29])#[N:9].C(OC([NH:39][C@:40]12[CH2:48][NH:47][CH2:46][C@@H:45]1[CH2:44][O:43][CH2:42][CH2:41]2)=O)(C)(C)C>C(#N)C>[NH2:39][C@:40]12[CH2:48][N:47]([C:11]3[C:10]([C:8]#[N:9])=[C:19]4[C:14]([C:15](=[O:29])[C:16]([C:24]([OH:26])=[O:25])=[CH:17][N:18]4[C@@H:20]4[CH2:22][C@@H:21]4[F:23])=[CH:13][C:12]=3[F:30])[CH2:46][C@@H:45]1[CH2:44][O:43][CH2:42][CH2:41]2
Reactant: CC(C)(C)OC(=O)N[C@@]12CCOC[C@H]1CNC2
Reactant: CCOC(=O)c1cn([C@@H]2C[C@@H]2F)c2c(C#N)c(F)c(F)cc2c1=O
Solvent: CCN(CC)CC
Solvent: CC#N
Product: N#Cc1c(N2C[C@@H]3COCC[C@@]3(N)C2)c(F)cc2c(=O)c(C(=O)O)cn([C@@H]3C[C@@H]3F)c12
Temperature: 25 °C
Reaction time: 18 h
Yield: 45.2 %

Procedure:
Triethylamine (0.263 mL, 1.88 mmol) and ethyl 8-cyano-6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-1,4-dihydro-4-oxoquinoline-3-carboxylate (211 mg, 0.627 mmol) were added to a solution of (1S,6S)-1-tert-butoxycarbonylamino-4-oxa-8-azabicyclo[4.3.0]nonane (151 mg, 0.628 mmol) in acetonitrile (1.25 mL) in a nitrogen atmosphere. The mixture was stirred at room temperature for 18 hours. The reaction solution was concentrated under reduced pressure. Then, the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0→90:10→60:40→50:50→34:66→25:75→16:84). A 1 mol/L sodium hydroxide solution (1.94 mL) was added to a solution of the resulting residue in ethanol (2.42 mL) under ice-cooling, and the mixture was stirred at room temperature for one hour. A 10% citric acid solution (30 mL) was added to the reaction solution, followed by extraction with ethyl acetate (40 mL×1, 30 mL×1). The organic layer was washed with brine (45 mL) and then dried over anhydrous sodium sulfate and filtered. The filtrate was then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform:methanol=100:0→99:1→98:2). Trifluoroacetic acid (1.38 ml, 3 v/w) was added to a solution of 243 mg of the resulting residue in dichloromethane (4.58 mL) with stirring under ice-cooling, and the mixture was stirred at room temperature for 2.5 hours. The reaction solution was concentrated under reduced pressure. Then, hydrochloric acid at pH 1 was added to the resulting residue under ice-cooling, and the mixture was washed with chloroform (40 mL×3). The aqueous layer was adjusted to pH 12 with a 1 mol/L sodium hydroxide solution under ice-cooling. The basic solution was adjusted to pH 7.4 with 1 mol/L hydrochloric acid, followed by extraction with chloroform (100 mL×1, 70 mL×1, 50 mL×1). The organic layer was dried over anhydrous sodium sulfate and filtered, and then the filtrate was concentrated under reduced pressure. The aqueous layer was concentrated under reduced pressure. The resulting residue was dissolved in chloroform/methanol=10/1, and the insoluble material was removed by filtration (×2). The residues obtained from the organic layer and the aqueous layer were purified by PTLC (lower layer of chloroform/methanol/water=7/3/1), respectively. These were combined and dissolved in dichloromethane (20 mL), and dichloromethane was azeotropically removed with ethanol (three times). Ethanol (5 mL) was added to the resulting residue, and the mixture was ultrasonically treated and then cooled. The precipitated solid was collected by filtration, washed with ethanol and diethyl ether, and dried under reduced pressure at 60° C. to give 122 mg of the title compound.