Potassium Carbonate → 1-Chloro-4-(2,2-difluoroethoxy)-6-methoxyisoquinoline

HRID 1852142Notes

Reaction equation

HRID 1852142 reaction equation
C(=O)([O-])[O-].[K+].[K+].[Cl:7][C:8]1[C:17]2[C:12](=[CH:13][C:14]([O:18][CH3:19])=[CH:15][CH:16]=2)[C:11]([OH:20])=[CH:10][N:9]=1.Br[CH2:22][CH:23]([F:25])[F:24]>O>[Cl:7][C:8]1[C:17]2[C:12](=[CH:13][C:14]([O:18][CH3:19])=[CH:15][CH:16]=2)[C:11]([O:20][CH2:22][CH:23]([F:25])[F:24])=[CH:10][N:9]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1361862-Bromo-1,1-difluoroethaneHCID 71743058HCID 71743058, compound

Product 1

HCID 866832151-Chloro-4-(2,2-difluoroethoxy)-6-methoxyisoquinolineYield 82.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

Potassium carbonate (659 mg, 4.77 mmol) was added to a solution of 1-chloro-6-methoxyisoquinolin-4-ol (500 mg, 2.385 mmol) and 2-bromo-1,1-difluoroethane (346 mg, 2.385 mmol) and stirred for 3 hrs at 50° C. After 3 hrs, the reaction was diluted with water and extracted with EtOAc. The organic layer was washed with water (2×) followed by brine. The organic layer was collected, dried over MgSO4, filtered and evaporated to give the crude product 1-chloro-4-(2,2-difluoroethoxy)-6-methoxyisoquinoline (538 mg, 82%) as an orange solid. Crude material used as is in next step. MS: MS m/z 274.1(M++1).

Workup

  1. waitAfter 3 hrs
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with water (2×)
  4. customThe organic layer was collected
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-1b9b4e741392412e883965772ddfc913
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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