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

HRID 1430749Notes

Reaction equation

HRID 1430749 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 acid

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 brought 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 mol) 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 under reduced pressure. The residue is further purified by column chromatography on silica gel, eluting with 7% ethyl acetate in hexane to give 4′-chloro-4-ethylbiphen-3-ylboronic acid.

Workup

  1. customis brought to −78° C.
  2. additionis added dropwise over 30 minutes
  3. stirringthe reaction mixture is stirred for two hours
  4. additiononce the addition
  5. stirringis stirred for two hours
  6. concentrationThe mixture is concentrated
  7. customto remove most of the tetrahydrofuran
  8. additiondiluted with water
  9. extractionextracted with diethyl ether
  10. washThe organic extracts are washed with water and brine
  11. dry with materialdried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. customthe filtrate is evaporated under reduced pressure
  14. customThe residue is further purified by column chromatography on silica gel
  15. washeluting with 7% ethyl acetate in hexane

Sources & evidence

ORD record
ord-725e0f28c1474f268a27cc45af8aeb8a
Source dataset
uspto-grants-2015_01
Patent number
US08940913B2

Reaction notes

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