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

HRID 72253Notes

Reaction equation

HRID 72253 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][CH3:9].C([Li])CCC.C[O:23][B:24](OC)[O:25]C.Cl>O1CCCC1>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([C:4]2[CH:5]=[CH:6][C:7]([CH2:8][CH3:9])=[C:2]([B:24]([OH:25])[OH:23])[CH:3]=2)=[CH:11][CH:12]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8470Trimethyl borateHCID 594459053-Bromo-4'-chloro-4-ethylbiphenylHCID 178418339Butyllithium

Product 1

HCID 594459274'-Chloro-4-ethylbiphenyl-3-ylboronic acidYield 69.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

3-Bromo-4′-chloro-4-ethylbiphenyl (10 g, 0.03 mol) is dissolved in tetrahydrofuran (250 ml), and the temperature is cooled to −78° C. n-Butyllithium (1.33 molar solution in hexanes, 34.6 ml) is added dropwise over 30 minutes, maintaining the temperature at around −78° C. The reaction mixture is stirred for one and a half hours, then trimethylborate (4.9 g, 0.05 mole) is added dropwise and the reaction mixture is stirred for two hours. A solution of 2N aqueous hydrochloric acid (100 ml) is added dropwise, and once the addition is complete the mixture is stirred for two hours. The mixture is concentrated to remove most of the tetrahydrofuran, then diluted with water and extracted with diethyl ether. The organic extracts are washed with water and brine, combined, dried over anhydrous sodium sulfate, filtered and the filtrate is evaporated in vacuo. The residue is further purified by flash column chromatography on silica gel, eluting with 7% ethyl acetate in hexane to give 4′-chloro-4-ethylbiphen-3-ylboronic acid (5.4 g).

Workup

  1. additionis added dropwise over 30 minutes
  2. stirringthe reaction mixture is stirred for two hours
  3. additiononce the addition
  4. stirringis stirred for two hours
  5. concentrationThe mixture is concentrated
  6. customto remove most of the tetrahydrofuran
  7. additiondiluted with water
  8. extractionextracted with diethyl ether
  9. washThe organic extracts are washed with water and brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. customthe filtrate is evaporated in vacuo
  13. customThe residue is further purified by flash column chromatography on silica gel
  14. washeluting with 7% ethyl acetate in hexane

Sources & evidence

ORD record
ord-a7a48e34eb3c402f9536a3f39d33fe63
Source dataset
uspto-grants-2014_09
Patent number
US08828908B2

Reaction notes

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