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Cesium fluoride → 1,7-Difluoro-4-methoxyisoquinoline

HRID 2361613
Notes
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Reaction equation

HRID 2361613 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[C:5]([O:13][CH3:14])=[CH:4][N:3]=1.[F-:15].[Cs+]>CS(C)=O.O>[F:15][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[C:5]([O:13][CH3:14])=[CH:4][N:3]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 25953Cesium fluorideHCID 222502381-Chloro-7-fluoro-4-methoxyisoquinoline

Product 1

HCID 866858121,7-Difluoro-4-methoxyisoquinolineYield 49.8%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
145 °C

Procedure

To a solution of 1-chloro-7-fluoro-4-methoxyisoquinoline (3.7 g, 17.48 mmol) in DMSO was added cesium fluoride (10.26 g, 69.9 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 combined 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 (1.7 g, 49%) as white solid. 1H NMR (400 MHz, CD3OD): δ ppm 8.20-8.18 (m, 1H), 7.69-7.66 (m, 1H), 7.54-7.47 (m, 1H), 7.46 (s, 1H), 4.04 (s, 3H); 19F NMR: δ ppm 109.65 (1 F), −78.53 (1 F); MS: MS m/z 196.1 (M++1).

Workup

  1. customThe reaction vessel (Pressure tube) was sealed
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined 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-09ec7ed5cd84461995ca0103bb75d772
Source dataset
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08691757B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes