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

HRID 45207Notes

Reaction equation

HRID 45207 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 (10, 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 2). 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-1084423b357245748455875f1a38a7aa
Source dataset
uspto-grants-2013_09
Patent number
US08541449B2

Reaction notes

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