Boron trifluoride etherate → 4-Chloro-2-isopropylphenol

HRID 1913851Notes

Reaction equation

HRID 1913851 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([CH:9]([CH2:11]O)[CH3:10])[CH:3]=1.C([SiH](CC)CC)C.B(F)(F)F.CCOCC>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([CH:9]([CH3:11])[CH3:10])[CH:3]=1

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 12052TriethylsilaneHCID 66809148HCID 66809148, compound

Product 1

HCID 5933974-Chloro-2-isopropylphenolYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a −10° C. solution of 4-chloro-2-(hydroxypropan-2-yl)phenol (6.00 g, 32.15 mmol) in 100 mL of methylene chloride add triethylsilane (31.0 mL, 194.08 mmol) and boron trifluoride diethyl etherate (66 mL, 520.82 mmol) dropwise over a period of 10 minutes. Keep the reaction mixture cold and stir for an additional hour before quenching with aqueous sodium bicarbonate. Separate the mixture, and extract the aqueous phase with methylene chloride. Wash combined organic phases with aqueous sodium bicarbonate and brine, dry over anhydrous magnesium sulfate, filter, and concentrate to give a purple oil. Purify by flash chromatography using 25% ethyl acetate in hexanes to give 4.37 g (80%) of pure 4-chloro-2-isopropylphenol as a clear oil. 1H NMR (400 MHz, CDCl3) δ 7.15 (d, J=2.6 Hz, 1H), 7.01 (dd, J=8.5, 2.6 Hz, 1H), 6.66 (d, J=8.5 Hz, 1H), 4.77 (s, 1H), 3.17 (sept, 1H), 1.24 (d, J=6.9 Hz, 6H). 3C NMR (101 MHz, CDCl3) δ 151.26, 136.37, 126.56, 126.36, 125.81, 116.46, 27.14, 22.33. MS: m/e 171.

Workup

  1. custombefore quenching with aqueous sodium bicarbonate
  2. customSeparate the mixture
  3. extractionextract the aqueous phase with methylene chloride
  4. washWash
  5. dry with materialdry over anhydrous magnesium sulfate
  6. filtrationfilter
  7. concentrationconcentrate
  8. customto give a purple oil
  9. customPurify by flash chromatography

Sources & evidence

ORD record
ord-410488882bb344d28d2f84fe10c705d3
Source dataset
uspto-grants-2013_12
Patent number
US08609794B2

Reaction notes

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