p-Toluenesulfonic acid monohydrate → HCID 21996962, compound

HRID 1976323Notes

Reaction equation

HRID 1976323 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([OH:17])=[C:6]([CH:16]=1)[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[CH:10]=1)=O.[CH3:18][Mg]Cl.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCCC1.C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([OH:17])=[C:6]([C:7]([C:9]2[CH:10]=[C:11]([CH3:15])[CH:12]=[CH:13][CH:14]=2)=[CH2:18])[CH:16]=1

Participants

6

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 21996988HCID 21996988, compound2×HCID 178418332HCID 178418332, compound

Product 1

HCID 21996962HCID 21996962, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a cold solution (−78° C.) of 99 mg (0.3 mmol) of 5-bromo-2-hydroxy-3′-methylbenzophenone (Compound L) in 5 mL of tetrahydrofuran (under a blanket of argon) was added 1.0 mL (3.0 mmol) of methyl magnesium chloride (3M in tetrahydrofuran). With the addition, the solution turned yellowish-orange in color. The −78° C. bath was removed and the solution was allowed to warm to ambient temperature and stirred for 2 hours. The reaction mixture was concentrated in vacuo, extracted between ethyl acetate and sat. NH4Cl (aq.) solution and the layers were separated. The organic phase was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo to give crude 4-bromo-2-[(1-m-tolyl-1-hydroxy)ethyl]phenol as a yellow oil. The crude alcohol was dissolved in 2 mL of toluene, placed under a blanket of argon and 5.9 mg of p-toluene sulfonic acid monohydrate was added. The resultant mixture was heated at 70° C. for 45 minutes, cooled to ambient temperature and purified by flash chromatography (silica, 5% ethyl acetate in hexane) to give the title compound as a clear, colorless oil.

Workup

  1. additionWith the addition
  2. customThe −78° C. bath was removed
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. extractionextracted between ethyl acetate and sat. NH4Cl (aq.) solution
  5. customthe layers were separated
  6. washThe organic phase was washed with water and brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give crude 4-bromo-2-[(1-m-tolyl-1-hydroxy)ethyl]phenol as a yellow oil
  11. additionwas added
  12. temperaturecooled to ambient temperature
  13. custompurified by flash chromatography (silica, 5% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-0d0ac1134458458e9330431791b29582
Source dataset
uspto-grants-2001_05
Patent number
US06225494B1

Reaction notes

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