Cesium carbonate → (1S,1aS,6bR)-ethyl 5-((7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-4-yl)oxy)-1a,6b-dihydro-1H-cyclopropa[b]benzofuran-1-carboxylate

HRID 920114Notes

Reaction equation

[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C@@H:8]3[C@@H:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C@@H:7]3[C:6]=2[CH:16]=1.F[C:18]1[CH:27]=[CH:26][N:25]=[C:24]2[C:19]=1[CH2:20][CH2:21][C:22](=[O:28])[NH:23]2.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[O:28]=[C:22]1[NH:23][C:24]2[N:25]=[CH:26][CH:27]=[C:18]([O:1][C:2]3[CH:3]=[CH:4][C:5]4[O:9][C@@H:8]5[C@@H:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C@@H:7]5[C:6]=4[CH:16]=3)[C:19]=2[CH2:20][CH2:21]1

Participants

Conditions

Temperature: 120 °C

Procedure

The mixture of Intermediate III (400 mg, 1.8 mmol), 5-fluoro-3,4-dihydro-1,8-naphthyridin-2(1H)-one (250 mg, 1.5 mmol) and cesium carbonate (801 mg, 2.3 mol) in DMF (20 mL) was stirred at 120° C. for 2 hrs. The reaction was diluted with water (10 mL) and extracted with ethyl acetate (2×10 mL). The combined organic phase was washed with brine (20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluted with EtOAc:PE=3:1) to obtain the title compound (360 mg, 54.6%) as a white solid.

Workup

extractionextracted with ethyl acetate (2×10 mL)
washThe combined organic phase was washed with brine (20 mL)
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel chromatography (eluted with EtOAc:PE=3:1)

Sources & evidence

ORD record: ord-c0a7eb61456b435aa47e9f0577c87deb
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273046B2

Reaction notes

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