Phosphorus oxychloride → 3-(4-(Tert-butyl)phenyl)-1-chloro-6-methoxyisoquinoline

HRID 1852249

Reaction equation

HRID 1852249 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[NH:12][C:13](=O)[C:14]3[C:19]([CH:20]=2)=[CH:18][C:17]([O:21][CH3:22])=[CH:16][CH:15]=3)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].O=P(Cl)(Cl)[Cl:26]>>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[C:13]([Cl:26])[C:14]3[C:19]([CH:20]=2)=[CH:18][C:17]([O:21][CH3:22])=[CH:16][CH:15]=3)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 709790183-(4-(tert-butyl)phenyl)-6-methoxyisoquinolin-1(2H)-one

Product 1

HCID 866832693-(4-(Tert-butyl)phenyl)-1-chloro-6-methoxyisoquinolineYield 28%

Procedure

A solution of 3-(4-(tert-butyl)phenyl)-6-methoxyisoquinolin-1(2H)-one (0.7 g, 2.277 mmol) in POCl3 (7 ml) was refluxed for overnight. 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 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 (10% ethyl acetate in pet ether) to get desired compound (0.21 g, 28.0%) as solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 8.34(s, 1H), 8.18-8.16 (d, J=8 Hz, 1H), 8.08-8.06 (d, J=8 Hz, 2H), 7.57-7.55 (d, J=8 Hz, 2H), 7.41 (s, 1H), 7.40-7.38 (d, J=8 Hz, 1H), 3.97 (s, 3H), 1.34 (s, 9H); MS: MS m/z 362.2 (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 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 (10% ethyl acetate in pet ether)

Sources & evidence

ORD record
ord-c0a156650a184eb2bbb2c3f68ed63fbc
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Linked notes

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