Iodine → HCID 57825194, compound

HRID 1668737Notes

Reaction equation

HRID 1668737 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:9][CH3:10])=[C:6]([CH3:8])[CH:7]=1.[Mg].II.[Br:14][C:15]1[CH:16]=[C:17]([C:22](=[O:24])[CH3:23])[CH:18]=[CH:19][C:20]=1[Cl:21]>O1CCCC1>[Br:14][C:15]1[CH:16]=[C:17]([C:22]([C:2]2[CH:3]=[CH:4][C:5]([O:9][CH3:10])=[C:6]([CH3:8])[CH:7]=2)([OH:24])[CH3:23])[CH:18]=[CH:19][C:20]=1[Cl:21]

Participants

6

Reactant 4

HCID 807Iodine2×HCID 6083154-Bromo-1-methoxy-2-methylbenzeneHCID 5462224MagnesiumHCID 133472831-(3-Bromo-4-chlorophenyl)ethan-1-one

Product 1

HCID 57825194HCID 57825194, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

5-Bromo-2-methoxytoluene (6.4 g, 0.032 mol) was dissolved in tetrahydrofuran (100 mL) and 5 mL of the solution was added to a stirred mixture of magnesium turnings (0.90 g, 0.037 mol) and iodine (a catalytic amount) in tetrahydrofuran (10 mL). The mixture was heated to vigorous reflux until some of the iodine colour was lost. The flask was removed from the heat and the remainder of the bromide was added so as to maintain a gentle reflux. The flask was then returned to the heat and stirred at reflux for 2 hours. The flask was removed from the heat and a solution of 1-(3-bromo-4-chlorophenyl)-ethanone (7.1 g, 0.030 mol) in tetrahydrofuran (100 mL) was added so as to maintain a gentle reflux. The reaction mixture was returned to the heat and stirred at reflux for 3 hours then cooled to room temperature and poured into ice-water (300 mL). The mixture was stirred for 5 minutes then concentrated to remove tetrahydrofuran. The aqueous residue was diluted with aqueous ammonium chloride (100 mL), extracted with ethyl acetate (3 200 mL) and the combined organic extracts were washed with water (100 mL) and brine (100 mL), dried (sodium sulfate) and concentrated to give the crude product as a red oil which was purified by flash chromatography (5 to 10% ethyl acetate/hexane) to give the desired alcohol as a bright yellow oil (6.7 g, 71%). 1H NMR (300 MHz; CDCl3) 7.72 (1H, d, J 2.1, Ar), 7.35 (1H, d, 8.5, Ar), 7.23-7.13 (3H, m, Ar), 6.76 (1H, d, J 8.5, Ar), 3.82 (3H, s, OMe), 2.19 (3H, s, Me), 2.11 (1H, s, OH), 1.88 (3H, s, Me).

Workup

  1. temperatureThe mixture was heated
  2. customThe flask was removed from the
  3. temperatureheat
  4. additionthe remainder of the bromide was added so as
  5. temperatureto maintain a gentle reflux
  6. temperatureheat
  7. temperatureat reflux for 2 hours
  8. customThe flask was removed from the
  9. temperatureheat
  10. temperatureto maintain a gentle reflux
  11. temperatureheat
  12. stirringstirred
  13. temperatureat reflux for 3 hours
  14. stirringThe mixture was stirred for 5 minutes
  15. concentrationthen concentrated
  16. customto remove tetrahydrofuran
  17. additionThe aqueous residue was diluted with aqueous ammonium chloride (100 mL)
  18. extractionextracted with ethyl acetate (3 200 mL)
  19. washthe combined organic extracts were washed with water (100 mL) and brine (100 mL)
  20. dry with materialdried (sodium sulfate)
  21. concentrationconcentrated
  22. customto give the crude product as a red oil which
  23. customwas purified by flash chromatography (5 to 10% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-ada7217573b24f209f399ad10f406ed9
Source dataset
uspto-grants-2011_08
Patent number
US07989449B2

Reaction notes

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