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

HRID 72296Notes

Reaction equation

HRID 72296 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

A solution of n-butyl lithium in hexanes (1.6 M, 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 hrs 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 hrs
  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-e5f00d4ba9c5490387c752c74da29b91
Source dataset
uspto-grants-2014_09
Patent number
US08828908B2

Reaction notes

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