Cesium fluoride → 1-Fluoro-4-methoxyisoquinoline

HRID 2361599Notes

Reaction equation

HRID 2361599 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][CH3:13])=[CH:4][N:3]=1.[F-:14].[Cs+]>CS(C)=O.O>[F:14][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][CH3:13])=[CH:4][N:3]=1

Participants

5

Reactant 2

HCID 25953Cesium fluorideHCID 222501441-Chloro-4-methoxyisoquinoline

Product 1

HCID 709791001-Fluoro-4-methoxyisoquinolineYield 62%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
145 °C

Procedure

To a solution of 1-chloro-4-methoxyisoquinolin (2.5 g, 12.91 mmol) in DMSO was added cesium fluoride (4.01 g, 25.82 mmol) at room temperature. The reaction vessel (Pressure tube) was sealed and heated at 145° C. for 18 h. The reaction mass was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure to get crude compound. The crude compound was purified by silica gel chromatography to get desired compound (700 mg, 62%) as a white solid. 1H NMR (400 MHz, CD3OD): δ ppm 8.10 (m, 1H), 8.08 (m, 1H), 7.78-7.75 (m, 1H), 7.69-7.65 (m, 1H), 7.49 (m, 1H), 4.04 (s, 3H); 19F NMR: δ ppm −78.66 (1 F); MS: MS m/z 178.1 (M++1).

Workup

  1. customThe reaction vessel (Pressure tube) was sealed
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. customevaporated under reduced pressure
  5. customto get crude compound
  6. customThe crude compound was purified by silica gel chromatography

Sources & evidence

ORD record
ord-37bffa0965074afd87a442e3ae256b69
Source dataset
uspto-grants-2014_04
Patent number
US08691757B2

Reaction notes

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