Cesium carbonate → 1-Chloro-4-cyclopropoxy-7-fluoroisoquinoline

HRID 1852219Notes

Reaction equation

HRID 1852219 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[C:5]([OH:13])=[CH:4][N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH:20]1(Br)[CH2:22][CH2:21]1>CN(C=O)C.O>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[C:5]([O:13][CH:20]2[CH2:22][CH2:21]2)=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 78037BromocyclopropaneHCID 717427161-Chloro-7-fluoroisoquinolin-4-OL

Product 1

HCID 717427171-Chloro-4-cyclopropoxy-7-fluoroisoquinolineYield 20%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
145 °C

Procedure

To a solution of 1-chloro-7-fluoroisoquinolin-4-ol (1 g, 5.06 mmol) in DMF (5 mL) was added Cs2CO3 (4.95 g, 15.18 mmol) followed by cyclopropyl bromide (1.2 mL, 15.18 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 (0.24 g, 20%) as a yellow solid.

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-90e4ba75d2634f249bc70efed15c7a96
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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