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

HRID 1430742Notes

Reaction equation

HRID 1430742 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([CH3:15])=[C:12](Br)[CH:13]=2)=[CH:4][CH:3]=1.C([Li])CCC.C[O:22][B:23](OC)[O:24]C.Cl>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([CH3:15])=[C:12]([B:23]([OH:24])[OH:22])[CH:13]=2)=[CH:4][CH:3]=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 acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

5-(4-chlorophenyl)-2-methyl-1-bromobenzene (5.0 g, 0.02 mol) is dissolved in tetrahydrofuran (125 ml), and the temperature is brought 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 under reduced pressure 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 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-methylbiphen-3-ylboronic acid.

Workup

  1. customis brought to −78° C.
  2. additionis added dropwise over 30 minutes
  3. stirringthe reaction mixture stirred for three and a half hours
  4. temperatureto warm to 0° C
  5. additiononce the addition
  6. stirringis stirred for 2 hours
  7. concentrationThe mixture is concentrated under reduced pressure
  8. customto remove most of the tetrahydrofuran
  9. additiondiluted with water (˜80 ml)
  10. extractionextracted with diethyl ether
  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-7da0ac05b18f4890939739419c58bb51
Source dataset
uspto-grants-2015_01
Patent number
US08940913B2

Reaction notes

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