Phosphorus oxychloride → 1-Chloro-6-methyl-5-nitroisoquinoline

HRID 1051247Notes

Reaction equation

HRID 1051247 reaction equation
[CH3:1][C:2]1[C:3]([N+:13]([O-:15])=[O:14])=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N+:7]([O-])[CH:6]=[CH:5]2.O=P(Cl)(Cl)[Cl:18]>ClCCCl>[Cl:18][C:8]1[C:9]2[C:4](=[C:3]([N+:13]([O-:15])=[O:14])[C:2]([CH3:1])=[CH:11][CH:10]=2)[CH:5]=[CH:6][N:7]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 673410166-Methyl-5-nitroisoquinoline 2-oxide

Product 1

HCID 226222211-Chloro-6-methyl-5-nitroisoquinolineYield 55.2%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

6-Methyl-5-nitroquinoline (46.5 g, 0.228 mol) obtained in Step (3) was dissolved in 1,2-dichloroethane (1.8 L), added with POCl3 (107 mL, 1.14 mol) at room temperature, and refluxed for 7 hours or more. The reaction solution was cooled to room temperature and concentrated by distilling the solvent under reduced pressure. The concentrated solid was dissolved in dichloromethane, added with an ice water, and extracted with dichloromethane. The combined organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrated solid was added with a mixed solution of ethyl acetate/hexane=1/1 (v/v), and stirred for 2 hours or more at room temperature. The solid thus obtained was filtered under reduced pressure, and washed with a mixed solution of ethyl acetate/hexane=1/1 (v/v). The filtered solid was dried with warm wind in an oven (40° C.) for over 3 hours or more to obtain the title compound (28 g, 55%).

Workup

  1. temperaturerefluxed for 7 hours or more
  2. concentrationconcentrated
  3. distillationby distilling the solvent under reduced pressure
  4. dissolutionThe concentrated solid was dissolved in dichloromethane
  5. additionadded with an ice water
  6. extractionextracted with dichloromethane
  7. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. additionThe concentrated solid was added with a mixed solution of ethyl acetate/hexane=1/1 (v/v)
  11. customThe solid thus obtained
  12. filtrationwas filtered under reduced pressure
  13. washwashed with a mixed solution of ethyl acetate/hexane=1/1 (v/v)
  14. customThe filtered solid was dried
  15. temperaturewith warm wind in an oven (40° C.) for over 3 hours or more

Sources & evidence

ORD record
ord-b5c6fa787a6f4afa9674a2d5e9f4bd4d
Source dataset
uspto-grants-2016_07
Patent number
US09388165B2

Reaction notes

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