Toluene → 7-amino-1-methyl-3,4-dihydroquinolin-2(1H)-one

HRID 2264323Notes

Reaction equation

HRID 2264323 reaction equation
C1(C)C=CC=CC=1.[CH3:8][N:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16](C(O)=O)[CH:17]=2)[CH2:12][CH2:11][C:10]1=[O:22].C1(P([N:37]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C(O)(C)(C)C>C(N(CC)CC)C>[NH2:37][C:16]1[CH:17]=[C:18]2[C:13]([CH2:12][CH2:11][C:10](=[O:22])[N:9]2[CH3:8])=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 6386tert-ButanolHCID 199401P,P-Diphenylphosphinic azideHCID 231122721-Methyl-2-oxo-1,2,3,4-tetrahydroquinoline-7-carboxylic acid

Product 1

HCID 336993947-amino-1-methyl-3,4-dihydroquinolin-2(1H)-oneYield 46.6%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

Into 10 ml of toluene was suspended 200 mg of 1-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-7-carboxylic acid, and then 268 mg of diphenylphosphoryl azide (DPPA), 722 mg of tert-butyl alcohol, and 0.135 ml of triethylamine were added thereto, followed by 14 hours of stirring under reflux with heating. After cooling, the reaction solution was concentrated under reduced pressure, water was added to the residue, and the organic layer was extracted with ethyl acetate. After the organic layer was dried over anhydrous sodium sulfate, the solvent was removed by evaporation. To the residue was added 5 ml of a 4M ethyl acetate solution of hydrochloric acid, followed by 7 hours of stirring at room temperature. Then, the reaction solution was concentrated under reduced pressure. To the residue was added a saturated aqueous sodium hydrogen carbonate, and the organic layer was extracted with chloroform. After the organic layer was dried over anhydrous sodium sulfate, the solvent was removed by evaporation. The obtained residue was purified by silica gel column chromatography (chloroform:methanol:aqueous ammonia) to obtain 80 mg of 7-amino-1-methyl-3,4-dihydroquinolin-2(1H)-one as a white solid.

Workup

  1. temperatureunder reflux
  2. temperaturewith heating
  3. temperatureAfter cooling
  4. concentrationthe reaction solution was concentrated under reduced pressure, water
  5. additionwas added to the residue
  6. extractionthe organic layer was extracted with ethyl acetate
  7. dry with materialAfter the organic layer was dried over anhydrous sodium sulfate
  8. customthe solvent was removed by evaporation
  9. additionTo the residue was added 5 ml of a 4M ethyl acetate solution of hydrochloric acid
  10. waitfollowed by 7 hours
  11. stirringof stirring at room temperature
  12. concentrationThen, the reaction solution was concentrated under reduced pressure
  13. additionTo the residue was added a saturated aqueous sodium hydrogen carbonate
  14. extractionthe organic layer was extracted with chloroform
  15. dry with materialAfter the organic layer was dried over anhydrous sodium sulfate
  16. customthe solvent was removed by evaporation
  17. customThe obtained residue was purified by silica gel column chromatography (chloroform:methanol:aqueous ammonia)

Sources & evidence

ORD record
ord-ed5b690f7df8400b8212827ee89efd7c
Source dataset
uspto-grants-2010_12
Patent number
US07855198B2

Reaction notes

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