Dimethylformamide → 3-Chloroisoquinoline-4-carbaldehyde

HRID 1471698Notes

Reaction equation

HRID 1471698 reaction equation
O=P(Cl)(Cl)[Cl:3].C[N:7]([CH:9]=O)[CH3:8].C1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][C:13](=[O:21])N1.[OH-].[Na+]>C1COCC1.C1(C)C=CC=CC=1>[Cl:3][C:8]1[N:7]=[CH:9][C:20]2[C:15]([C:14]=1[CH:13]=[O:21])=[CH:16][CH:17]=[CH:18][CH:19]=2

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 904691,4-dihydro-2H-isoquinolin-3-one

Product 1

HCID 145672793-Chloroisoquinoline-4-carbaldehydeYield 50%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of POCl3 (0.73 mL, 7.85 mmol, 3.8 eqiv.) and DMF (0.6 g, 8.16 mmol, 4.0 equiv.) in THF was added 1,2-dihydroisoquinolin-3-(4H)-one at 0° C. in portions for 5 min. The mixture was continued to stir at 0° C. for 1 h and poured into a mixture of 2 N NaOH (20 mL), ice (20 g), and toluene (20 mL). The organic phase was separated and the aqueous layer was extracted with toluene one more time. The combined organic layer was washed with water, dried over Na2SO4, and concentrated to half of its volume at low temperature in vacuo. To this mixture was added 2 N H2SO4 (20 mL) under vigorous stirring followed by ground KMnO4 in portions. The mixture was continued to stir for another 4 h. The organic phase was separated, dried over Na2SO4, and concentrated to give 3-chloroisoquinoline-4-carbaldehyde (220 mg, 50% pure) as a oil, which was used for next step without further purification. LRMS (M+H+) m/z 192.0.

Workup

  1. customThe organic phase was separated
  2. extractionthe aqueous layer was extracted with toluene one more time
  3. washThe combined organic layer was washed with water
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to half of its volume at low temperature in vacuo
  6. additionTo this mixture was added 2 N H2SO4 (20 mL)
  7. stirringunder vigorous stirring
  8. stirringto stir for another 4 h
  9. customThe organic phase was separated
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-d707d1c0d1834c8ebbcc4ac35a46efb3
Source dataset
uspto-grants-2015_04
Patent number
US09012450B2

Reaction notes

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