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

HRID 43323Notes

Reaction equation

HRID 43323 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>C1COCC1>[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 acidYield 50.7%

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 THF (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 around −78° C. The reaction mixture is stirred for one and half hours at −78° C., then trimethylborate (2.58 g, 0.024 mol) is added dropwise and the reaction mixture stirred for three and 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 5-(4-chlorophenyl)-2-methylphenylboronic acid (2.5 g).

Workup

  1. customis brought to −78° C.
  2. additionis added dropwise over 30 minutes
  3. stirringthe reaction mixture stirred for three and half hours
  4. temperatureto warm to 0° C
  5. additiononce the addition
  6. stirringis stirred for 2 hours
  7. concentrationThe mixture is concentrated in vacuo
  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 evaporated in vacuo
  14. customThe residue is further purified by flash column chromatography on silica gel
  15. washeluting with 7% ethyl acetate in hexane

Sources & evidence

ORD record
ord-23992b5e78f84bbcb795534a57b8ef97
Source dataset
uspto-grants-2013_09
Patent number
US08536351B2

Reaction notes

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