Phosphorus oxychloride → 1-Chloro-7-fluoro-4-methoxyisoquinoline

HRID 2361612Notes

Reaction equation

HRID 2361612 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:13][CH3:14])=[CH:7][NH:8][C:9]2=O)=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:17]>>[Cl:17][C:9]1[C:10]2[C:5](=[CH:4][CH:3]=[C:2]([F:1])[CH:11]=2)[C:6]([O:13][CH3:14])=[CH:7][N:8]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 222502317-Fluoro-4-methoxyisoquinolin-1-OL

Product 1

HCID 222502381-Chloro-7-fluoro-4-methoxyisoquinolineYield 24%

Procedure

A solution of 7-fluoro-4-methoxyisoquinolin-1(2H)-one (11 g, 56.9 mmol) in POCl3 (100 ml) was refluxed for 18 h. The solvent was evaporated under reduced pressure and the residue was diluted with cold water. The aqueous solution was basified by solid sodium carbonate and extracted with ethyl acetate. The combine organic layer was dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to get crude compound. The crude compound was purified by silica gel chromatography (20% ethyl acetate in pet ether) to get desired compound (2.9 g, 24%) as off-white solid. 1H NMR (400 MHz, CDCl3): δ ppm 8.36-8.32 (m, 1H), 7.93-7.90 (m, 1H), 7.88 (s, 1H), 7.70-7.65 (m, 1H), 4.11 (s, 3H); MS: MS m/z 212.1 (M++1).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. additionthe residue was diluted with cold water
  3. extractionextracted with ethyl acetate
  4. dry with materialThe combine organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customto get crude compound
  8. customThe crude compound was purified by silica gel chromatography (20% ethyl acetate in pet ether)

Sources & evidence

ORD record
ord-446add8215fc470c84b89013f3dbed66
Source dataset
uspto-grants-2014_04
Patent number
US08691757B2

Reaction notes

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