Sodium Hydroxide → (2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)boronic acid

HRID 1473282Notes

Reaction equation

HRID 1473282 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[C:12]1[N:16]([CH3:17])[N:15]=[CH:14][CH:13]=1.[B:18](OC(C)C)([O:23]C(C)C)[O:19]C(C)C.C([Li])CCC.[OH-].[Na+]>O.C(OCC)C>[CH3:17][N:16]1[C:12]([C:3]2[CH:4]=[C:5]([C:8]([F:11])([F:10])[F:9])[CH:6]=[CH:7][C:2]=2[B:18]([OH:23])[OH:19])=[CH:13][CH:14]=[N:15]1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 21531Triisopropyl borateHCID 712595845-(2-bromo-5-(trifluoromethyl)phenyl)-1-methyl-1H-pyrazole2×HCID 178418339Butyllithium

Product 1

HCID 71258947(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)boronic acidYield 90.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

An 250 mL round-bottom flask was charged with 5-(2-bromo-5-(trifluoromethyl)phenyl)-1-methyl-1H-pyrazole (Intermediate F) (2.956 g, 9.69 mmol), diethyl ether (74.5 mL), and triisopropyl borate (2.70 mL, 11.63 mmol). The flask was cooled to −78° C. for 10 min, after which butyllithium (2.5M in hexanes) (4.65 mL, 11.63 mmol) was added dropwise. The mixture was stirred for 30 min, and then warmed to room temperature. A 2N aq. NaOH solution (100 mL) was added, and the resulting biphasic mixture was stirred vigorously for 1 h. The mixture was diluted with water, and the layers separated. The ethereal layer was extracted with water (twice) and the water layers were combined and washed with diethyl ether. The ether layers were back-extracted once more, and all aqueous layers combined and acidified to a pH of about 2 with 6N aq. HCl to give a clear solution. The aqueous layer was extracted with ethyl acetate (twice), and the combined organics were dried over sodium sulfate, filtered and concentrated. The residue was concentrated from DCM to give (2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)boronic acid (2.36 g, 8.74 mmol) as a yellow solid. m/z (ESI) 271.2 (M+H)+.

Workup

  1. temperaturewarmed to room temperature
  2. stirringthe resulting biphasic mixture was stirred vigorously for 1 h
  3. customthe layers separated
  4. extractionThe ethereal layer was extracted with water (twice) and the water layers
  5. washwashed with diethyl ether
  6. extractionThe ether layers were back-extracted once more
  7. customto give a clear solution
  8. extractionThe aqueous layer was extracted with ethyl acetate (twice), and the combined
  9. dry with materialorganics were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. concentrationThe residue was concentrated from DCM

Sources & evidence

ORD record
ord-9bb0790b0a574efc8fd8a0b51e6f79c9
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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