Sodium hydride → 5-Chloro-6-(1,4-dioxa-spiro[4.5]dec-8-yloxy)-isoquinoline

HRID 2370735Notes

Reaction equation

HRID 2370735 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([OH:11])[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[H-].[Na+].[Cl:14][C:15]1[C:24](F)=[CH:23][CH:22]=[C:21]2[C:16]=1[CH:17]=[CH:18][N:19]=[CH:20]2>CN(C=O)C>[Cl:14][C:15]1[C:24]([O:11][CH:8]2[CH2:9][CH2:10][C:5]3([O:4][CH2:3][CH2:2][O:1]3)[CH2:6][CH2:7]2)=[CH:23][CH:22]=[C:21]2[C:16]=1[CH:17]=[CH:18][N:19]=[CH:20]2

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 5673521,4-Dioxaspiro(4.5)decan-8-ol2×HCID 59818261Isoquinoline, 5-chloro-6-fluoro-

Product 1

HCID 592685835-Chloro-6-(1,4-dioxa-spiro[4.5]dec-8-yloxy)-isoquinoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

887 mg (5.61 mmol) 1,4-Dioxa-spiro[4.5]decan-8-ol were dissolved in 50 ml DMF and 224 mg (5.61 mmol) sodium hydride (60%) were added. After stirring for 30 minutes at room temperature, a solution of 815 mg (4.49 mmol) 5-chloro-6-fluoro-isoquinoline (8) in 10 ml DMF was added and the mixture was heated to 100° C. After 4 h one additional equivalent of 1,4-dioxa-spiro[4.5]decan-8-ol and sodium hydride were added and stirring was continued at 100° C. After 1.5 h complete conversion could be detected. For working up, the solvent was removed under reduced pressure, the residue was taken up in H2O and extracted three times with ethyl acetate. The combined organic layers were dried over MgSO4 and evaporated. The obtained orange oil (2.17 g) was stirred in diisopropyl ether and the insoluble white precipitate was filtered off. After drying of the precipitate, 549 mg of the title compound could be isolated. Rt=1.15 min (Method #1). Detected mass: 320.1/322.1 (M+H+).

Workup

  1. temperaturethe mixture was heated to 100° C
  2. stirringstirring
  3. customwas continued at 100° C
  4. waitAfter 1.5 h complete conversion could be detected
  5. customthe solvent was removed under reduced pressure
  6. extractionextracted three times with ethyl acetate
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. customevaporated
  9. stirringThe obtained orange oil (2.17 g) was stirred in diisopropyl ether
  10. filtrationthe insoluble white precipitate was filtered off
  11. dry with materialAfter drying of the precipitate, 549 mg of the title compound
  12. customcould be isolated

Sources & evidence

ORD record
ord-33f6720e1dc0428393ae95b5864e035a
Source dataset
uspto-grants-2014_04
Patent number
US08710228B2

Reaction notes

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