Sulfuric Acid → 1-{3-[7-(3-Hydroxy-2-hydroxymethyl-propoxy)-6-methoxy-quinolin-4-yloxy]-quinolin-2-yl}-ethanone

HRID 228998Notes

Reaction equation

HRID 228998 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][C:13]3[C:14]([C:23](=[O:25])[CH3:24])=[N:15][C:16]4[C:21]([CH:22]=3)=[CH:20][CH:19]=[CH:18][CH:17]=4)=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:26][CH3:27].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC1(C)[O:53][CH2:52][CH:51]([CH2:54]O)[CH2:50][O:49]1.CCOC(/N=N/C(OCC)=O)=O.S(=O)(=O)(O)O.[OH-].[Na+]>O1CCCC1.O>[OH:49][CH2:50][CH:51]([CH2:52][OH:53])[CH2:54][O:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][C:13]3[C:14]([C:23](=[O:25])[CH3:24])=[N:15][C:16]4[C:21]([CH:22]=3)=[CH:20][CH:19]=[CH:18][CH:17]=4)=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:26][CH3:27]

Participants

9

Reactant 6

HCID 1118Sulfuric AcidHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 3584869(2,2-Dimethyl-1,3-dioxan-5-yl)methanolHCID 5462977Diethyl azodicarboxylateHCID 136131623HCID 136131623, compound2×

Product 1

HCID 577564981-{3-[7-(3-Hydroxy-2-hydroxymethyl-propoxy)-6-methoxy-quinolin-4-yloxy]-quinolin-2-yl}-ethanoneYield 75.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-[3-(7-Hydroxy-6-methoxy-quinolin-4-yloxy)-quinolin-2-yl]-ethanone (compound 390) (50 mg) was dissolved in tetrahydrofuran (1 ml) to prepare a solution. Triphenylphosphine (73 mg), (2,2-dimethyl-[1,3]dioxan-5-yl)-methanol (24 mg), and diethylazodicarboxylate (0.05 ml) were added to the solution, and the mixture was stirred at room temperature for 4 hr. Further, 1 N sulfuric acid (3 ml) was added thereto, and the mixture was stirred at room temperature overnight. The reaction solution was brought to 0° C. and was stirred. The reaction solution was made alkaline by the addition of a 10% aqueous sodium hydroxide solution. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with saturated brine and was 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 (47 mg, yield 75%).

Workup

  1. customto prepare a solution
  2. stirringthe mixture was stirred at room temperature overnight
  3. customwas brought to 0° C.
  4. stirringwas stirred
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe ethyl acetate layer was then washed with saturated brine
  7. dry with materialwas dried over anhydrous sodium sulfate
  8. customThe solvent was removed by distillation under the reduced pressure
  9. customthe residue was purified by thin layer chromatography

Sources & evidence

ORD record
ord-5440563cc4f1419cb962a95689fd5eae
Source dataset
uspto-grants-2009_07
Patent number
US07560558B2

Reaction notes

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