Water → HCID 86614796, compound

HRID 1361460Notes

Reaction equation

HRID 1361460 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]1[C:12]([O:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=2)=[CH:11][CH:10]=[C:9]2[C:4]=1[C:5]([OH:27])=[C:6]([CH3:26])[C:7]([CH3:25])=[N:8]2.[H-].[Na+].[CH:32]1([C:35](Cl)=[O:36])[CH2:34][CH2:33]1.O>CN(C)C=O>[CH:32]1([C:35]([O:27][C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:12]([O:13][C:14]4[CH:19]=[CH:18][C:17]([O:20][C:21]([F:23])([F:22])[F:24])=[CH:16][CH:15]=4)[C:3]=3[C:2]([F:28])([F:1])[F:29])[N:8]=[C:7]([CH3:25])[C:6]=2[CH3:26])=[O:36])[CH2:34][CH2:33]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 77637Cyclopropanecarbonyl chlorideHCID 178432214HCID 178432214, compound

Product 1

HCID 86614796HCID 86614796, compoundYield 39.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Trifluoromethyl-6-(4-trifluoromethoxyphenoxy)-4-hydroxy-2,3-dimethyl-quinoline (30 mg) prepared in Synthesis Example 3 was dissolved in 1 mL of dimethylformamide. Under ice cooling, 4.3 mg of 60% sodium hydride was added to the solution, and the mixture was stirred for one hr. Thereafter, 10.4 mg of cyclopropanecarbonyl chloride was added thereto, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was added to 5 mL of water, and the mixture was extracted with 5 mL of ethyl acetate. The ethyl acetate layer was washed with a saturated sodium hydrogencarbonate solution and saturated brine, was dried over anhydrous sodium sulfate, and was then concentrated under the reduced pressure. The crude product thus obtained was purified by chromatography on silica gel (Mega Bond Elut SI (Varian) 10 mL, solvent: n-hexane/ethyl acetate) to give 4-Cyclopropanecarbonyloxy-2,3-dimethyl-6-(4-trifluoromethoxyphenoxy)-5-trifluoromethyl-quinoline (13.8 mg, yield 39.5%).

Workup

  1. stirringthe mixture was stirred at room temperature for 3 hr
  2. extractionthe mixture was extracted with 5 mL of ethyl acetate
  3. washThe ethyl acetate layer was washed with a saturated sodium hydrogencarbonate solution and saturated brine
  4. dry with materialwas dried over anhydrous sodium sulfate
  5. concentrationwas then concentrated under the reduced pressure
  6. customThe crude product thus obtained
  7. customwas purified by chromatography on silica gel (Mega Bond Elut SI (Varian) 10 mL, solvent: n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-c0af63b2641143deb72ae78dae010128
Source dataset
uspto-grants-2011_02
Patent number
US07880006B2

Reaction notes

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