p-Toluenesulfonic acid → HCID 178437464, compound

HRID 1361462Notes

Reaction equation

HRID 1361462 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([CH3:24])[C:8]=1[O:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=1)[NH2:5].[CH3:25][CH:26]([C:31](=O)[CH2:32][CH3:33])[C:27](OC)=[O:28].C1(C)C=CC(S(O)(=O)=O)=CC=1.O.C(=O)(O)[O-].[Na+]>C1(C)C(C)=CC=CC=1.C(OCC)(=O)C>[CH2:32]([C:31]1[C:26]([CH3:25])=[C:27]([OH:28])[C:6]2[C:4](=[CH:3][C:2]([CH3:1])=[C:8]([O:9][CH2:10][CH2:11][CH2:12][O:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:22])([F:21])[F:23])=[CH:16][CH:15]=3)[C:7]=2[CH3:24])[N:5]=1)[CH3:33]

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 545860Methyl 2-methyl-3-oxopentanoateHCID 66921909HCID 66921909, compoundHCID 86585896Sodium bicarbonate water

Product 1

HCID 178437464HCID 178437464, compoundYield 91.6%

Reagents, catalysts & solvents 2

HCID 7237O-XyleneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1.18 g of 3,5-dimethyl-4-(3-(4-trifluoromethylphenoxy)propoxy)aniline, 1.35 g of methyl 2-methyl-3-oxopentanoate, and 0.7 g of p-toluenesulfonic acid dissolved in 38 mL of xylene was heated under reflux for 7 hr. This reaction solution was cooled, and ethyl acetate and sodium bicarbonate water were added thereto, followed by separation. The ethyl acetate layer was washed with brine and was further concentrated under the reduced pressure to give 1.38 g of 2-ethyl-4-hydroxy-3,5,7-trimethyl-6-(3-(4-trifluoromethylphenoxy)propoxy)quinoline. Next, 1.38 g of the product thus obtained was added to 15 mL of dimethylacetamide, and 0.26 g of 60% sodium hydride and 0.6 g of methyl chloroformate were added thereto at room temperature. The reaction solution was stirred at room temperature for 2 hr, and ethyl acetate and distilled water were then added thereto. The organic layer was washed with brine and was 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) and was then recrystallized from n-hexane /ethyl acetate to give 1.13 g of 4-methoxycarbonyloxy-2-ethyl-3,5,7-trimethyl-6-(3-(4-trifluoromethylphenoxy)propoxy)quinoline (yield 72.2%).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 7 hr
  3. temperatureThis reaction solution was cooled
  4. customfollowed by separation
  5. washThe ethyl acetate layer was washed with brine
  6. concentrationwas further concentrated under the reduced pressure

Sources & evidence

ORD record
ord-271b46c8a0ee47a1b41051710711cbda
Source dataset
uspto-grants-2011_02
Patent number
US07880006B2

Reaction notes

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