Hydrochloric Acid → 4'-Chloro-3-methylbiphen-4-ylboronic acid

HRID 341681Notes

Reaction equation

HRID 341681 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)=[CH:9][C:8]=1[CH3:20].[B:21](OC)([O:24]C)[O:22]C.Cl>O1CCCC1>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([C:10]2[CH:9]=[C:8]([CH3:20])[C:7]([B:21]([OH:24])[OH:22])=[CH:12][CH:11]=2)=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8470Trimethyl borateHCID 594505164-Bromo-4'-chloro-3-methylbiphenylHCID 178418339Butyllithium

Product 1

HCID 594504934'-Chloro-3-methylbiphen-4-ylboronic acidYield 59.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

n-Butyl lithium (1.6 M solution in hexanes, 37.5 ml, 0.060 mol) is added dropwise to a solution of 4-bromo-4′-chloro-3-methylbiphenyl (11.5 g, 0.041 mol) in tetrahydrofuran (120 ml) at −78° C., under an atmosphere of nitrogen, and the mixture is stirred at −78° C. for 30 minutes. Trimethyl borate (27.4 ml, 0.245 mol) is added slowly at −78° C. and the mixture is stirred for 1 hr. The reaction mixture is allowed to warm to room temperature over 2-3 hours and then stirred at room temperature for 1 hr. 0.1N Aqueous hydrochloric acid (320 ml) is added and the mixture is stirred at room temperature overnight. The reaction mixture is extracted with ethyl acetate (3×300 ml) and the organic extracts are combined, dried with anhydrous sodium sulfate, filtered and the filtrate is concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give 4′-chloro-3-methylbiphen-4-ylboronic acid (6.0 g) as white solid.

Workup

  1. stirringthe mixture is stirred for 1 hr
  2. temperatureto warm to room temperature over 2-3 hours
  3. stirringstirred at room temperature for 1 hr
  4. stirringthe mixture is stirred at room temperature overnight
  5. extractionThe reaction mixture is extracted with ethyl acetate (3×300 ml)
  6. dry with materialdried with anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate is concentrated under reduced pressure
  9. customThe residue is purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-f8491472caa346e185240b41242fb8b2
Source dataset
uspto-grants-2014_11
Patent number
US08895761B2

Reaction notes

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