p-Toluenesulfonic acid → HCID 178437462, compound

HRID 1361461Notes

Reaction equation

HRID 1361461 reaction equation
[Cl:1][C:2]1[C:3]([O:12][C:13]2[C:19]([CH3:20])=[CH:18][C:16]([NH2:17])=[CH:15][C:14]=2[CH3:21])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH3:22][CH:23]([C:28](=O)[CH2:29][CH3:30])[C:24](OC)=[O:25].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C(C)=CC=CC=1>[Cl:1][C:2]1[C:3]([O:12][C:13]2[C:19]([CH3:20])=[C:18]3[C:16](=[CH:15][C:14]=2[CH3:21])[N:17]=[C:28]([CH2:29][CH3:30])[C:23]([CH3:22])=[C:24]3[OH:25])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:9])[F:10])[CH:7]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 545860Methyl 2-methyl-3-oxopentanoateHCID 66921931HCID 66921931, compound

Product 1

HCID 178437462HCID 178437462, compound

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

A solution of 1.52 9 of 4-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-3,5-dimethylaniline, 1.75 g of methyl 2-methyl-3-oxopentanoate, and 0.92 g of p-toluenesulfonic acid dissolved in 49 mL of xylene was heated under reflux for 8 hr. This reaction solution was cooled, and the precipitated crystals were then collected by filtration and were washed with n-hexane and distilled water and were dried to give 2.56 g of 6-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-2-ethyl-4-hydroxy-3,5,7-trimethyl-quinoline. Dimethylacetamide (30 mL) was then added to 1.97 g of the crystals thus obtained, and 0.38 g of 60% sodium hydride and 0.9 g of methyl chloroformate were added thereto at room temperature. The mixture was stirred at room temperature for 2 hr, and ethyl acetate and distilled water were then added. The organic layer was washed with brine and was then concentrated under the reduced pressure. The crude product was purified by column chromatography on silica gel (BW300, manufactured by Fuji Sylysia Chemical Ltd., solvent: n-hexane /ethyl acetate) to give 1.25 g of 4-methoxycarbonyloxy-6-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-2-ethyl-3,5,7-trimethylquinoline (yield 55.6%).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 8 hr
  3. temperatureThis reaction solution was cooled
  4. filtrationthe precipitated crystals were then collected by filtration
  5. washwere washed with n-hexane
  6. distillationdistilled water
  7. customwere dried

Sources & evidence

ORD record
ord-2f6bdb3515034253bfe0a72361a1843e
Source dataset
uspto-grants-2011_02
Patent number
US07880006B2

Reaction notes

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