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

HRID 1473306Notes

Reaction equation

HRID 1473306 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]1[N:13]([CH3:14])[N:12]=[CH:11][CH:10]=1.[B:15](OC(C)C)([O:20]C(C)C)[O:16]C(C)C.[Li]CCCC.[OH-].[Na+]>O.C(OCC)C>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([B:15]([OH:20])[OH:16])=[C:3]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][CH:10]=2)[CH:4]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 21531Triisopropyl borateHCID 712594035-(2-bromo-5-chlorophenyl)-1-methyl-1H-pyrazoleHCID 178418339Butyllithium

Product 1

HCID 71258743(4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)boronic acidYield 76.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×

Procedure

A 50-mL round-bottom flask was charged with 5-(2-bromo-5-chlorophenyl)-1-methyl-1H-pyrazole (992.0 mg, 3.65 mmol), diethyl ether (18 mL), and triisopropyl borate (1 mL, 4.38 mmol). The flask was cooled in a dry ice-acetone bath for 10 min, then n-BuLi (1.91 mL, 4.38 mmol) was added dropwise over a couple of minutes. Following the addition, the cooling bath was removed, and the mixture was warmed to room temperature. An aq. 2N NaOH solution (20 mL, 40 mmol) was added, and the resulting mixture was stirred vigorously for 2 h. The mixture was diluted with water and diethyl ether. The layers were separated, and the ethereal layer was extracted with water (twice). The aq. layers were combined, and the combined aq. mixture as washed with diethyl ether. The etheral layer was back-extracted once more, and the aq. layers were all combined. The combined aq. solution was acidified to about pH 1 with 3N aq. HCl to give a clear solution. The aq. solution was extracted with EtOAc (three times), and the combined organic extracts were dried over sodium sulfate, filtered and concentrated. The residue was taken up in DCM and concentrated under a vacuum to give (4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)boronic acid (660 mg, 2.79 mmol) as a light-yellow foam. m/z (ESI) 237.0 (M+H)+.

Workup

  1. temperatureThe flask was cooled in a dry ice-acetone bath for 10 min
  2. additionthe addition
  3. customthe cooling bath was removed
  4. customThe layers were separated
  5. extractionthe ethereal layer was extracted with water (twice)
  6. washthe combined aq. mixture as washed with diethyl ether
  7. extractionThe etheral layer was back-extracted once more
  8. customto give a clear solution
  9. extractionThe aq. solution was extracted with EtOAc (three times)
  10. dry with materialthe combined organic extracts were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. concentrationconcentrated under a vacuum

Sources & evidence

ORD record
ord-d8c00592d31344828dbb70a89a20882b
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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