Hydrochloric Acid → HCID 69423782, compound

HRID 350115Notes

Reaction equation

HRID 350115 reaction equation
[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:41]=[CH:40][C:18]([CH2:19][N:20]2[CH:24]=[C:23]([CH2:25][CH2:26][C:27]([O:29]CC)=[O:28])[C:22](OS(C(F)(F)F)(=O)=O)=[N:21]2)=[CH:17][CH:16]=1.[F:42][C:43]([F:54])([F:53])[C:44]1[CH:49]=[CH:48][C:47](B(O)O)=[CH:46][CH:45]=1.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+].Cl>O1CCCC1.C(O)C.C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:16]=[CH:17][C:18]([CH2:19][N:20]2[CH:24]=[C:23]([CH2:25][CH2:26][C:27]([OH:29])=[O:28])[C:22]([C:47]3[CH:48]=[CH:49][C:44]([C:43]([F:54])([F:53])[F:42])=[CH:45][CH:46]=3)=[N:21]2)=[CH:40][CH:41]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 86760425HCID 86760425, compound

Product 1

HCID 69423782HCID 69423782, compoundYield 22%

Reagents, catalysts & solvents 4

HCID 702EthanolSolvent2×HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Tetrakis(triphenolphosphine)palladium (120 mg) was added to a mixture of ethyl 3-[1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-trifluoromethanesulfonyloxy-1H-pyrazol-4-yl]propionate (1.20 g), 4-trifluoromethylphenylboronic acid (0.46 g), 2N aqueous sodium carbonate solution (2.6 ml), ethanol (3 ml), and toluene (50 ml). This mixture was refluxed under an argon atmosphere for 13 hours. Ethyl acetate was added to the reaction mixture, and the mixture was washed with saturated aqueous sodium chloride solution, dried (MgSO4), then concentrated. The residue was subjected to silica gel column chromatography, and a colorless oily substance was obtained from the fraction eluted with ethyl acetate-hexane (1:3, volume ratio). A mixture of the oily substance obtained, 1N aqueous sodium hydroxide solution (5 ml), ethanol (5 ml) and tetrahydrofuran (5 ml) was stirred at room temperature for 2 hours. The reaction mixture was acidified with dilute hydrochloric acid, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), then concentrated. The colorless crystals obtained were collected by filtration to yield 3-[1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-(4-trifluoromethylphenyl)-1H-pyrazol-4-yl]propionic acid (250 mg, yield: 22%). This was recrystallized from ethyl acetate-hexane. Melting point: 149–150° C.

Workup

  1. temperatureThis mixture was refluxed under an argon atmosphere for 13 hours
  2. washthe mixture was washed with saturated aqueous sodium chloride solution
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customa colorless oily substance was obtained from the fraction
  6. washeluted with ethyl acetate-hexane (1:3, volume ratio)
  7. additionA mixture of the oily substance
  8. customobtained
  9. extractionwas extracted with ethyl acetate
  10. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride solution
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated
  13. customThe colorless crystals obtained
  14. filtrationwere collected by filtration

Sources & evidence

ORD record
ord-dca1854a112e440daaed71290f5a293d
Source dataset
uspto-grants-2007_02
Patent number
US07179823B1

Reaction notes

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