Sulfuric Acid → 2-[6-Methoxy-4-(6-methyl-2-thiazol-2-yl-pyridin-3-yloxy)-quinolin-7-yloxymethyl]-propane-1,3-diol

HRID 228930Notes

Reaction equation

HRID 228930 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]([C:22]2[S:23][CH:24]=[CH:25][N:26]=2)=[N:17][C:18]([CH3:21])=[CH:19][CH:20]=1.CC1(C)[O:33][CH2:32][CH:31]([CH2:34]O)[CH2:30][O:29]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N=C=NN=NN=C=NCC)C.S(=O)(=O)(O)O>C1(C)C=CC=CC=1.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:34][CH:31]([CH2:32][OH:33])[CH2:30][OH:29])[N:9]=[CH:8][CH:7]=[C:6]2[O:14][C:15]1[C:16]([C:22]2[S:23][CH:24]=[CH:25][N:26]=2)=[N:17][C:18]([CH3:21])=[CH:19][CH:20]=1

Participants

8

Reactant 5

HCID 1118Sulfuric AcidHCID 11776TriphenylphosphineHCID 3584869(2,2-Dimethyl-1,3-dioxan-5-yl)methanolHCID 86605188DiethylazocarbodiimideHCID 1358548316-Methoxy-4-(6-methyl-2-thiazol-2-yl-pyridin-3-yloxy)-quinolin-7-ol2×

Product 1

HCID 577563622-[6-Methoxy-4-(6-methyl-2-thiazol-2-yl-pyridin-3-yloxy)-quinolin-7-yloxymethyl]-propane-1,3-diolYield 19%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

Toluene (0.4 ml) was added to 6-methoxy-4-(6-methyl-2-thiazol-2-yl-pyridin-3-yloxy)-quinolin-7-ol (compound 329) (20 mg) and (2,2-dimethyl[1,3]dioxan-5-yl)-methanol (24 mg). Triphenylphosphine (43 mg) and a solution of diethylazocarbodiimide (29 mg) in toluene (0.2 ml) were added in that order to the mixture, and the mixture was stirred at room temperature for 4 hr. A 1 N aqueous sulfuric acid solution (1 ml) was added to the reaction solution, and the mixture was stirred at room temperature overnight. Water was added to the reaction solution, the mixture was washed with ethyl acetate, and the ethyl acetate layer was extracted with 1 N hydrochloric acid. Aqueous layers were combined, the combined aqueous layers were made alkaline by the addition of potassium carbonate, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water 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 (4.7 mg, yield 19%).

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. washthe mixture was washed with ethyl acetate
  3. extractionthe ethyl acetate layer was extracted with 1 N hydrochloric acid
  4. additionby the addition of potassium carbonate
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe ethyl acetate layer was washed with water
  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-7c1d9aced1bc4270bf45c218639a57c4
Source dataset
uspto-grants-2009_07
Patent number
US07560558B2

Reaction notes

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