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

HRID 1465149Notes

Reaction equation

HRID 1465149 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 CH2C2 (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 CH2C2 (250 mL×3)
  2. washThe organic layer was washed with saturated a.q
  3. dry with materialNaHCO3, dried over MgSO4
  4. customevaporated under vacuum
  5. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-faa46e0d1eb94c42b32c4931f5b326fb
Source dataset
uspto-grants-2015_04
Patent number
US08999976B2

Reaction notes

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