Sulfuric Acid → 4-Fluoro-2-(1-methylcyclohexyl)phenol

HRID 471983

Reaction equation

HRID 471983 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[CH3:9][C:10]1(O)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.S(=O)(=O)(O)O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([C:10]2([CH3:9])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:3]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 97324-FluorophenolHCID 115501-Methylcyclohexanol

Product 1

HCID 593949974-Fluoro-2-(1-methylcyclohexyl)phenol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Fluorophenol (41.8 g, 373 mmol) and 1-methylcyclohexanol (63.8 g, 560 mmol) dissolved in 600 mL of dried CH2Cl2, were treated with concentrated sulfuric acid (98%, 22.3 mL, 418 mmol). The mixture was stirred at room temperature for 50 hours. The reaction mixture was then extracted by CH2C1-2(250 mL×3). The organic layer was washed with saturated a.q NaHCO3., dried over MgSO4, and evaporated under vacuum. The residue was purified by column chromatography on silica gel to give 4-fluoro-2-(1-methylcyclohexyl)phenol as a dark green oil—47.6 g. 1H NMR (400 MHz, CDCl3) δ 7.00 (dd, J=3.2, 11.2 Hz, 1H), 6.76-6.71 (m, 1H), 6.62-6.59 (m, 1H), 5.27 (brs, 1H), 2.13-2.07 (m, 2H), 1.70-1.37 (m, 8H), 1.32 (s, 3H).

Workup

  1. extractionThe reaction mixture was then extracted by CH2C1-2(250 mL×3)
  2. washThe organic layer was washed with saturated a.q NaHCO3
  3. dry with material, dried over MgSO4
  4. customevaporated under vacuum
  5. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-db3d9cd99f544b9f835beba3e5c7602e
Source dataset
uspto-grants-2014_01
Patent number
US08633189B2

Linked notes

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