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

HRID 341687Notes

Reaction equation

HRID 341687 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[CH2:20][CH3:21].[B:22](OC)([O:25]C)[O:23]C.Cl>O1CCCC1>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([C:10]2[CH:9]=[C:8]([CH2:20][CH3:21])[C:7]([B:22]([OH:25])[OH:23])=[CH:12][CH:11]=2)=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8470Trimethyl borateHCID 594505094-Bromo-4'-chloro-3-ethylbiphenylHCID 178418339Butyllithium

Product 1

HCID 594504924'-Chloro-3-ethylbiphen-4-ylboronic acidYield 42.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

n-Butyl lithium (1.6 M solution in hexanes, 38.75 ml, 0.062 mol) is added dropwise to a solution of 4-bromo-4′-chloro-3-ethylbiphenyl (12.35 g, 0.041 mol) in tetrahydrofuran (125 ml) at −78° C., under an atmosphere of nitrogen, and the mixture is stirred at −78° C. for 30 minutes. Trimethyl borate (27.8 ml, 0.25 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 (343 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-ethylbiphen-4-ylboronic acid (4.5 g) as a 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-369caeb7b42645e5bd30c1bb80df2b08
Source dataset
uspto-grants-2014_11
Patent number
US08895761B2

Reaction notes

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