Dimethylformamide → HCID 57756426, compound

HRID 228987Notes

Reaction equation

HRID 228987 reaction equation
CN(C)C=[O:4].[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][C:17]=1[OH:18])[N:14]=[CH:13][CH:12]=[C:11]2[O:19][C:20]1[C:21]([CH3:30])=[N:22][C:23]2[C:28]([CH:29]=1)=[CH:27][CH:26]=[CH:25][CH:24]=2.C(=O)([O-])[O-].[K+].[K+].[CH2:37]([C@@H:39]1[O:41][CH2:40]1)Cl>O>[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][C:17]=1[O:18][CH2:37][C@H:39]([OH:41])[CH2:40][OH:4])[N:14]=[CH:13][CH:12]=[C:11]2[O:19][C:20]1[C:21]([CH3:30])=[N:22][C:23]2[C:28]([CH:29]=1)=[CH:27][CH:26]=[CH:25][CH:24]=2

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 2734062(-)-EpichlorohydrinHCID 1358548286-Methoxy-4-(2-methyl-quinolin-3-yloxy)-quinolin-7-ol2×

Product 1

HCID 57756426HCID 57756426, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

N,N-Dimethylformamide (3 ml) was added to 6-methoxy-4-(2-methyl-quinolin-3-yloxy)-quinolin-7-ol (compound 352) (100 mg), potassium carbonate (125 mg), and (R)-epichlorohydrin (124 mg), and the mixture was stirred at 70° C. overnight. The reaction solution was cooled to room temperature, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and was then dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure. The residue was dissolved in dichloromethane (3 ml), trifluoroacetic acid (3 ml) was added dropwise to the solution at 0° C., and the mixture was then stirred at room temperature for 3 hr. The reaction solution was made alkaline by the addition of a 1 N aqueous sodium hydroxide solution, and the mixture was extracted with chloroform. The chloroform layer was washed with water and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using chloroform-methanol to give the title compound (24 mg, yield 76%).

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe ethyl acetate layer was washed with water
  4. dry with materialwas then dried over anhydrous sodium sulfate
  5. customthe solvent was removed by distillation under the reduced pressure
  6. dissolutionThe residue was dissolved in dichloromethane (3 ml)
  7. additiontrifluoroacetic acid (3 ml) was added dropwise to the solution at 0° C.
  8. stirringthe mixture was then stirred at room temperature for 3 hr
  9. additionby the addition of a 1 N aqueous sodium hydroxide solution
  10. extractionthe mixture was extracted with chloroform
  11. washThe chloroform layer was washed with water
  12. dry with materialwas then dried over anhydrous sodium sulfate
  13. customThe solvent was removed by distillation under the reduced pressure
  14. customthe residue was purified by thin layer chromatography

Sources & evidence

ORD record
ord-01df4459674b4c929036e7198d45a90a
Source dataset
uspto-grants-2009_07
Patent number
US07560558B2

Reaction notes

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