Tetrahydrofuran → [4-(3-Hydroxypentan-3-yl)-2-methylphenyl]boronic acid

HRID 1443328Notes

Reaction equation

HRID 1443328 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:13])([CH2:11][CH3:12])[CH2:9][CH3:10])=[CH:4][C:3]=1[CH3:14].O1CCCC1.C([Li])CCC.[B:25](OC(C)C)([O:30]C(C)C)[O:26]C(C)C>CCCCCC>[CH2:9]([C:8]([C:5]1[CH:6]=[CH:7][C:2]([B:25]([OH:30])[OH:26])=[C:3]([CH3:14])[CH:4]=1)([OH:13])[CH2:11][CH3:12])[CH3:10]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 21531Triisopropyl borateHCID 574330783-(4-Bromo-3-methyl-phenyl)-pentan-3-olHCID 178418339Butyllithium

Product 1

HCID 59167146[4-(3-Hydroxypentan-3-yl)-2-methylphenyl]boronic acidYield 71%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Conditions

Temperature
-70 °C

Procedure

In a three-necked flask, introduce under nitrogen 5 g of 3-(4-bromo-3-methylphenyl)pentan-3-ol (19.4 mmol) and 50 cm3 of tetrahydrofuran. Cool the mixture to −70° C. and add dropwise 23.3 cm3 (58 mmol) of a 2.5M solution of n-butyllithium in hexane, over 30 minutes. Leave the mixture for approximately 2 h with stirring at −70° C. and then add dropwise 13.5 cm3 of triisopropyl borate (58 mmol), over 20 minutes. Leave the mixture with stirring for 3 h, allowing the temperature to increase to −10° C. Hydrolyse the mixture with saturated NH4Cl solution and extract two times with ethyl acetate. Wash the combined organic phases with saturated sodium chloride solution and dry them over sodium sulfate. Evaporate the solvents under vacuum. This gives 5 g of a colorless oil, which is chromatographed on silica gel (heptane/ethyl acetate=9/1) to give 4-(1-ethyl-1-hydroxypropyl)-2-methylphenylboronic acid in the form of a highly viscous oil. (Yield=71%)

Workup

  1. customLeave the mixture for approximately 2 h
  2. waitover 20 minutes
  3. customLeave the mixture
  4. stirringwith stirring for 3 h
  5. temperatureto increase to −10° C
  6. extractionHydrolyse the mixture with saturated NH4Cl solution and extract two times with ethyl acetate
  7. washWash the combined organic phases with saturated sodium chloride solution
  8. dry with materialdry them over sodium sulfate
  9. customEvaporate the solvents under vacuum
  10. customThis gives 5 g of a colorless oil, which is chromatographed on silica gel (heptane/ethyl acetate=9/1)

Sources & evidence

ORD record
ord-aea31dcd9fb0419facdcf05b3aeedaba
Source dataset
uspto-grants-2010_02
Patent number
US07659421B2

Reaction notes

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