Dimethylacetamide → 7-Chloro-6-hydroxy-1-methoxyisoquinoline

HRID 1948168Notes

Reaction equation

HRID 1948168 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]=[C:9]2[O:12][CH3:13])=[CH:4][C:3]=1F.CC(N(C)C)=[O:17]>O>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]=[C:9]2[O:12][CH3:13])=[CH:4][C:3]=1[OH:17]

Participants

4

Reactant 2

HCID 31374DimethylacetamideHCID 583808287-Chloro-6-fluoro-1-methoxyisoquinoline

Product 1

HCID 1361750037-Chloro-6-hydroxy-1-methoxyisoquinoline

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

A solution of sodium trimethylsilanoate (149.2 mL, 1M in THF) was added to a solution of 7-chloro-6-fluoro-1-methoxyisoquinoline (4, 10 g, 47.2 mmol) in DMA (200 mL) under argon. After stirring at 60° C. for 24 hours, the solution was evaporated under reduced pressure and then freeze dried to give crude product (20.4 g). This was dissolved in water and the pH adjusted to pH=6.5. A light brown precipitate was collected by filtration and purified by reverse phase chromatography (0 to 4 minutes, 15% acetonitrile/water, 4 to 24 minutes 15 to 90% acetonitrile/water and then 100% acetonitrile) to give 7 g of the desired product Rt=2.60 min (Method C). Detected mass: 210.0 (M+H+).

Workup

  1. customthe solution was evaporated under reduced pressure
  2. customfreeze dried
  3. customto give crude product (20.4 g)
  4. filtrationA light brown precipitate was collected by filtration
  5. custompurified by reverse phase chromatography (0 to 4 minutes, 15% acetonitrile/water, 4 to 24 minutes 15 to 90% acetonitrile/water

Sources & evidence

ORD record
ord-746d4314d31d4bc788a3deca4345dc46
Source dataset
uspto-grants-2013_03
Patent number
US08399482B2

Reaction notes

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