Hydrochloric Acid → 5-(4-Chlorophenyl)-2-methylphenylboronic acid

HRID 1470837Notes

Reaction equation

HRID 1470837 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[CH3:8].C([Li])CCC.C[O:22][B:23](OC)[O:24]C.Cl>O1CCCC1>[Cl:15][C:12]1[CH:13]=[CH:14][C:9]([C:4]2[CH:5]=[CH:6][C:7]([CH3:8])=[C:2]([B:23]([OH:24])[OH:22])[CH:3]=2)=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8470Trimethyl borateHCID 594459301-Bromo-5-(4-chlorophenyl)-2-methylbenzeneHCID 178418339Butyllithium

Product 1

HCID 594459235-(4-Chlorophenyl)-2-methylphenylboronic acidYield 50.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

3-Bromo-4′-chloro-4-methylbiphenyl (5.0 g, 0.02 mol) is dissolved in anhydrous tetrahydrofuran (125 ml), and the mixture is cooled to −78° C. n-Butyllithium (1.33 molar solution in hexanes, 17.3 ml,) is added dropwise over 30 minutes, maintaining the temperature at approximately −78° C. The reaction mixture is stirred for one and a half hours at −78° C., then trimethylborate (2.58 g, 0.024 mol) is added dropwise and the reaction mixture stirred for three and a half hours, allowing it to warm to 0° C. A solution of 2N aqueous hydrochloric acid (50 ml) is then added dropwise, and once the addition is complete the mixture is stirred for 2 hours. The mixture is concentrated in vacuo to remove most of the tetrahydrofuran, then diluted with water (˜80 ml) and extracted with diethyl ether. The organic extracts are combined, dried over anhydrous sodium sulfate, filtered and the filtrate 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-methylbiphenyl-3-ylboronic acid (2.5 g).

Workup

  1. additionis added dropwise over 30 minutes
  2. stirringthe reaction mixture stirred for three and a half hours
  3. temperatureto warm to 0° C
  4. additiononce the addition
  5. stirringis stirred for 2 hours
  6. concentrationThe mixture is concentrated in vacuo
  7. customto remove most of the tetrahydrofuran
  8. additiondiluted with water (˜80 ml)
  9. extractionextracted with diethyl ether
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. customthe filtrate 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-a191528ecafc4c12bf5fba86111e88db
Source dataset
uspto-grants-2015_04
Patent number
US09006429B2

Reaction notes

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