Reaction SMILES: C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.Br[C:44]1[C:53]([CH3:54])=[C:52]2[C:47]([C:48](=[O:64])[C:49]([C:59]([O:61]CC)=[O:60])=[CH:50][N:51]2[C@@H:55]2[CH2:57][C@@H:56]2[F:58])=[CH:46][C:45]=1[F:65].C(OC([NH:73][C@@:74]12[CH2:80][CH2:79][C@:78]1([F:81])[CH2:77][NH:76][CH2:75]2)=O)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].[OH-].[Na+]>O1CCOCC1.O.C(O)C.Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:73][C@@:74]12[CH2:80][CH2:79][C@:78]1([F:81])[CH2:77][N:76]([C:44]1[C:53]([CH3:54])=[C:52]3[C:47]([C:48](=[O:64])[C:49]([C:59]([OH:61])=[O:60])=[CH:50][N:51]3[C@@H:55]3[CH2:57][C@@H:56]3[F:58])=[CH:46][C:45]=1[F:65])[CH2:75]2
Reactant: CCOC(=O)c1cn([C@@H]2C[C@@H]2F)c2c(C)c(Br)c(F)cc2c1=O
Reactant: CC(C)(C)OC(=O)N[C@@]12CC[C@]1(F)CNC2
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: Cl
Solvent: CCO
Solvent: C1COCCO1
Solvent: O
Product: Cc1c(N2C[C@]3(N)CC[C@]3(F)C2)c(F)cc2c(=O)c(C(=O)O)cn([C@@H]3C[C@@H]3F)c12
Temperature: 95 °C
Reaction time: 14 h
Yield: 56.3 %

Procedure:
To a solution of tris(dibenzylideneacetone)dipalladium (0) (414 mg, 0.452 mmol) and 4,5-bis(diphenyl)phosphino-9,9-dimethylxanthene (522 mg, 0.902 mmol) in 1,4-dioxane (20.0 ml) were added ethyl 7-bromo-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylate (1.28 g, 3.31 mmol), (1R,5S)-1-(tert-butoxycarbonyl amino)-5-fluoro-3-azabicyclo[3.2.0]heptane (693 mg, 3.01 mmol) and cesium carbonate (1.96 g, 6.02 mmol) and the mixture was stirred at 95° C. for 14 hours under nitrogen atmosphere. The reaction mixture was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The organic layer was dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane-ethyl acetate; 100:0→95:5→90:10→75:25→5:95→0:100) to afford a pale yellow solid. To a solution of this solid in ethanol (15.9 ml) was added 1 mol/l aqueous solution of sodium hydroxide (5.98 ml) in an ice bath and the mixture was stirred at room temperature for 13 hours. To this reaction solution was added 1 mol/l aqueous solution of hydrochloric acid (5.98 ml) in an ice bath and the organic layer was concentrated under reduced pressure. The aqueous solution was diluted with water (80 ml) and extracted with ethyl acetate (100 ml×1, 80 ml×1). The organic layer was dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform-methanol; 100:0→99:1→98:2→97:3→96:4→95:5→94:6→93:7) to afford a pale yellow solid. The solid was dissolved in concentrated hydrochloric acid (3.0 ml) in an ice bath and the aqueous solution was washed with chloroform (40 ml×4). To the aqueous layer was added saturated solution of sodium hydroxide to adjust pH to 12.0 and the basic aqueous solution was adjusted with hydrochloric acid to pH 7.4. The solution was extracted with chloroform (250 ml×4). The organic layer was dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by recrystallization from ethanol to afford the title compound 690 mg (56%) as pale yellow solid.