Phosphorus oxychloride → 1-Chloro-6-methoxy-4-phenylisoquinoline-3-carbonitrile

HRID 639889Notes

Reaction equation

HRID 639889 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=O)[NH:8][C:7]([C:14]#[N:15])=[C:6]2[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.O=P(Cl)(Cl)[Cl:24]>>[Cl:24][C:9]1[C:10]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:12][CH:11]=2)[C:6]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:7]([C:14]#[N:15])[N:8]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 112428516-Methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile

Product 1

HCID 114264141-Chloro-6-methoxy-4-phenylisoquinoline-3-carbonitrile

Procedure

A mixture of 6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile (200 mg) and POCl3 (10 mL) was heated to 90 C for 18 h. The reaction was concentrated, and the residue was dissolve in EtOAc, cooled to 0 C, and quenched by careful addition of saturated aqueous sodium bicarbonate. The mixture was partitioned between saturated aqueous sodium bicarbonate and EtOAc. The aqueous solution was washed twice with EtOAc. The combined organic solutions were dried (Na2SO4) and concentrated. Flash chromatography (25 g silica, 3-30% EA/hex) gave a white solid.

Workup

  1. temperaturewas heated to 90 C for 18 h
  2. concentrationThe reaction was concentrated
  3. dissolutionthe residue was dissolve in EtOAc
  4. temperaturecooled to 0 C
  5. customquenched by careful addition of saturated aqueous sodium bicarbonate
  6. customThe mixture was partitioned between saturated aqueous sodium bicarbonate and EtOAc
  7. washThe aqueous solution was washed twice with EtOAc
  8. dry with materialThe combined organic solutions were dried (Na2SO4)
  9. concentrationconcentrated
  10. customFlash chromatography (25 g silica, 3-30% EA/hex) gave a white solid

Sources & evidence

ORD record
ord-996e42d3d1794393a7211c4cee57b332
Source dataset
uspto-grants-2010_04
Patent number
US07691879B2

Reaction notes

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