Cesium carbonate → 8-Chloro-3-(2,2,2-trifluoroethoxy)-1,5-naphthyridine

HRID 1513808Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][N:5]=[C:6]2[C:11]=1[N:10]=[CH:9][C:8]([OH:12])=[CH:7]2.C(=O)([O-])[O-].[Cs+].[Cs+].FC(F)(F)S(O[CH2:25][C:26]([F:29])([F:28])[F:27])(=O)=O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][N:5]=[C:6]2[C:11]=1[N:10]=[CH:9][C:8]([O:12][CH2:25][C:26]([F:29])([F:28])[F:27])=[CH:7]2

Participants

Conditions

Temperature: 50 °C

Procedure

A resealable pressure bottle was charged with 8-chloro-1,5-naphthyridin-3-ol (80 mg, 0.44 mmol), cesium carbonate (433 mg, 1.3 mmol), 2,2,2-trifluoroethyl trifluoromethanesulfonate (360 mg, 1.55 mmol), and DMF (0.9 ml). Vessel sealed and placed in a pre-heated at 50° C. oil bath. Reaction allowed to stir at this temperature for 45 minutes. LC/MS shows complete conversion. Quench with water, dilute with aqueous sodium bicarbonate solution and dichloromethane. Layers separated, organic layer collected and dried over sodium sulfate. This was concentrated to afford yellow oil; which was purified by ISCO silica gel chromatography (20-40% EtOAc/Hexanes) to afford 8-chloro-3-(2,2,2-trifluoroethoxy)-1,5-naphthyridine (65 mg, 56% yield). MS [M+H][email protected] minutes. Calc'd for C10H6ClF3N2O=262.6.

Workup

customVessel sealed
customReaction
customQuench with water
additiondilute with aqueous sodium bicarbonate solution and dichloromethane
customLayers separated
customorganic layer collected
dry with materialdried over sodium sulfate
concentrationThis was concentrated
customto afford yellow oil
customwhich was purified by ISCO silica gel chromatography (20-40% EtOAc/Hexanes)

Sources & evidence

ORD record: ord-403546aaba9f4b69a23b7f0df3b5b809
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08217177B2

Reaction notes

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