Sodium Bicarbonate → t-butyl[4-(9-hydroxy-2-methyl-9-trifluoromethyl-9H-fluoren-4-yl)-pyrazol-1-yl]-acetate

HRID 1799042Notes

Reaction equation

HRID 1799042 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[N:11][N:12]([CH2:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:13]=2)O1.Cl[C:24]1[C:36]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:29]([C:38]([F:41])([F:40])[F:39])([OH:37])[C:28]=2[CH:27]=[C:26]([CH3:42])[CH:25]=1.C(=O)([O-])O.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:18]([O:17][C:15](=[O:16])[CH2:14][N:12]1[CH:13]=[C:9]([C:24]2[C:36]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[C:29]([OH:37])([C:38]([F:40])([F:41])[F:39])[C:28]=3[CH:27]=[C:26]([CH3:42])[CH:25]=2)[CH:10]=[N:11]1)([CH3:19])([CH3:20])[CH3:21]

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 59216326tert-Butyl 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)acetateHCID 59492563(+)-4-chloro-2-methyl-9-trifluoromethyl-9H-fluoren-9-ol

Product 1

HCID 59492691t-butyl[4-(9-hydroxy-2-methyl-9-trifluoromethyl-9H-fluoren-4-yl)-pyrazol-1-yl]-acetateYield 59.8%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 22272177Toluene waterSolvent

Conditions

Temperature
110 °C

Procedure

To a suspension of t-butyl [4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-acetate (24.8 g), (+)-4-chloro-2-methyl-9-trifluoromethyl-9H-fluoren-9-ol (20.0 g), and sodium hydrogen carbonate (11.3 g) in toluene/water (200 ml/60 ml) were added palladium acetate (750 mg) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (2.75 g) at room temperature and the mixture was stirred at 110° C. for 2 hr. To the reaction mixture were added water (80 ml) and activated carbon (2.0 g) at room temperature and the mixture was stirred for 1 hr. The mixture was filtered through celite, and the solid was washed with tetrahydrofuran (100 ml). The filtrate was partitioned and the aqueous layer was extracted with ethyl acetate (100 ml). The combined organic layer was successively washed twice with water (100 ml) and once with saturated brine (100 ml), anhydrous sodium sulfate and silica gel (40 g) were added, and the mixture was stirred overnight. The mixture was filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was treated with n-hexane/ethyl acetate (2/1, 120 ml) solution, and the resulting slurry was filtered to give the title compound (17.8 g).

Workup

  1. stirringthe mixture was stirred for 1 hr
  2. filtrationThe mixture was filtered through celite
  3. washthe solid was washed with tetrahydrofuran (100 ml)
  4. customThe filtrate was partitioned
  5. extractionthe aqueous layer was extracted with ethyl acetate (100 ml)
  6. washThe combined organic layer was successively washed twice with water (100 ml) and once with saturated brine (100 ml), anhydrous sodium sulfate and silica gel (40 g)
  7. additionwere added
  8. stirringthe mixture was stirred overnight
  9. filtrationThe mixture was filtered
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. additionThe obtained residue was treated with n-hexane/ethyl acetate (2/1, 120 ml) solution
  12. filtrationthe resulting slurry was filtered

Sources & evidence

ORD record
ord-d8380874d8d549e4be48716c8245c418
Source dataset
uspto-grants-2013_01
Patent number
US08343994B2

Reaction notes

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