Potassium Carbonate → 8-chloro-9-(difluoromethoxy)-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one

HRID 1398461Notes

Reaction equation

[Cl:1][C:2]1[C:3]([OH:19])=[CH:4][C:5]2[C:14]3[C:9](=[C:10]([CH3:15])[N:11]=[CH:12][CH:13]=3)[C:8](=[O:16])[N:7]([CH3:17])[C:6]=2[CH:18]=1.C([O-])([O-])=O.[K+].[K+].Cl[C:27]([F:32])([F:31])C([O-])=O.[Na+]>C(#N)C.O>[Cl:1][C:2]1[C:3]([O:19][CH:27]([F:32])[F:31])=[CH:4][C:5]2[C:14]3[C:9](=[C:10]([CH3:15])[N:11]=[CH:12][CH:13]=3)[C:8](=[O:16])[N:7]([CH3:17])[C:6]=2[CH:18]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To the stirred solution of 8-chloro-9-hydroxy-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (0.5 g, 1.456 mmol), prepared as described in Example 89, Part B in acetonitrile (5 mL) was added K2CO3 (0.604 g, 4.37 mmol) followed by sodium 2-chloro-2,2-difluoroacetate (0.444 g, 2.91 mmol). The mixture was heated to 80° C. for 18 h. After cooling, the reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (2×80 mL). The organic layer was washed with brine solution, dried over Na2SO4, filtered and concentrated under reduced pressure to afford 8-chloro-9-(difluoromethoxy)-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (50 mg, 0.154 mmol, 11% crude yield) as a semi solid. The material was carried on without further purification. LC/MS (ESI) m/e 325.0 [(M+H)+, calcd for C15H12ClF2N2O2 325.04]; LC/MS retention time (method C): tR=2.39 min.

Workup

temperatureAfter cooling
extractionextracted with ethyl acetate (2×80 mL)
washThe organic layer was washed with brine solution
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-47bcb37cdefb4128a32554e0f721a52a
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901305B2

Reaction notes

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