Hydrochloric Acid → 2-(1-ethyl-1H-pyrazol-4-yl)-9-hydroxy-9-trifluoromethyl-9H-fluorene-4-carboxylic acid

HRID 1799018Notes

Reaction equation

HRID 1799018 reaction equation
Cl[C:2]1[CH:14]=[C:13]([C:15]([OH:17])=[O:16])[C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([OH:22])([C:18]([F:21])([F:20])[F:19])[C:4]=2[CH:3]=1.[CH2:23]([N:25]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=[N:26]1)[CH3:24].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.Cl>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O.O1CCOCC1>[CH2:23]([N:25]1[CH:29]=[C:28]([C:2]2[CH:14]=[C:13]([C:15]([OH:17])=[O:16])[C:12]3[C:11]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[C:5]([OH:22])([C:18]([F:21])([F:19])[F:20])[C:4]=3[CH:3]=2)[CH:27]=[N:26]1)[CH3:24]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 113790451-Ethyl-1H-pyrazole-4-boronic acid, pinacol esterHCID 594927212-chloro-9-hydroxy-9-trifluoromethyl-9H-fluorene-4-carboxylic acid

Product 1

HCID 594931002-(1-ethyl-1H-pyrazol-4-yl)-9-hydroxy-9-trifluoromethyl-9H-fluorene-4-carboxylic acidYield 63.5%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Under an argon atmosphere, an optically active form (0.100 g) of 2-chloro-9-hydroxy-9-trifluoromethyl-9H-fluorene-4-carboxylic acid, 1-ethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.133 g), tripotassium phosphate (0.191 g), palladium(II)acetate (0.0034 g), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.0123 g), dioxane (3 ml) and water (0.6 ml) were mixed, and the mixture was stirred at 100° C. for 1 hr. The reaction mixture was cooled to room temperature, hydrochloric acid and ethyl acetate were added, and the mixture was partitioned in a separatory funnel. The organic layer was washed twice with water and once with saturated brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was treated with hexane/ethyl acetate mixed solution (hexane:ethyl acetate=1:2,2 ml). This slurry was filtered, and the obtained solid was dried to give the title compound (0.075 g, 63%).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customthe mixture was partitioned in a separatory funnel
  3. washThe organic layer was washed twice with water and once with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. additionthe obtained residue was treated with hexane/ethyl acetate mixed solution (hexane:ethyl acetate=1:2,2 ml)
  8. filtrationThis slurry was filtered
  9. customthe obtained solid was dried

Sources & evidence

ORD record
ord-28d12c2a72104d509f15b96d89ae4229
Source dataset
uspto-grants-2013_01
Patent number
US08343994B2

Reaction notes

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