Trifluoroacetic acid → 2,2-Bis-hydroxymethyl-3-[6-methoxy-4-(2-methyl-quinolin-3-yloxy)-quinolin-7-yloxy]-propan-1-ol

HRID 228989Notes

Reaction equation

HRID 228989 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[OH:13])[N:9]=[CH:8][CH:7]=[C:6]2[O:14][C:15]1[C:16]([CH3:25])=[N:17][C:18]2[C:23]([CH:24]=1)=[CH:22][CH:21]=[CH:20][CH:19]=2.C(=O)([O-])[O-].[K+].[K+].Br[CH2:33][C:34]([CH2:39][OH:40])([CH2:37][OH:38])[CH2:35][OH:36].FC(F)(F)C(O)=O.[OH-].[Na+]>O.CN(C)C=O>[OH:36][CH2:35][C:34]([CH2:39][OH:40])([CH2:33][O:13][C:12]1[CH:11]=[C:10]2[C:5]([C:6]([O:14][C:15]3[C:16]([CH3:25])=[N:17][C:18]4[C:23]([CH:24]=3)=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:2][CH3:1])[CH2:37][OH:38]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 879541,3-Propanediol, 2-(bromomethyl)-2-(hydroxymethyl)-HCID 1358548286-Methoxy-4-(2-methyl-quinolin-3-yloxy)-quinolin-7-ol2×

Product 1

HCID 577564442,2-Bis-hydroxymethyl-3-[6-methoxy-4-(2-methyl-quinolin-3-yloxy)-quinolin-7-yloxy]-propan-1-olYield 21%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

N,N-Dimethylformamide (1.5 ml) was added to 6-methoxy-4-(2-methyl-quinolin-3-yloxy)-quinolin-7-ol (compound 352) (50 mg), potassium carbonate (62 mg), and 2-bromomethyl-2-hydroxymethyl-propane-1,3-diol (90 mg), and the mixture was stirred at 80° 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. The solvent was removed by distillation under the reduced pressure, and the residue was dissolved in dichloromethane (3 ml) to prepare a solution. 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 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 (14 mg, yield 21%).

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. customto prepare a solution
  8. stirringthe mixture was then stirred at room temperature for 3 hr
  9. extractionwas extracted with chloroform
  10. washThe chloroform layer was washed with water
  11. dry with materialwas then dried over anhydrous sodium sulfate
  12. customThe solvent was removed by distillation under the reduced pressure
  13. customthe residue was purified by thin layer chromatography

Sources & evidence

ORD record
ord-42f744f4d1844e79a641dce6153fc873
Source dataset
uspto-grants-2009_07
Patent number
US07560558B2

Reaction notes

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