4-Bromoanisole → 1-Benzyl-4-(4-methoxyphenyl)piperidin-4-ol

HRID 1417814Notes

Reaction equation

HRID 1417814 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.[Mg].[CH2:11]([N:18]1[CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C1COCC1>[CH2:11]([N:18]1[CH2:23][CH2:22][C:21]([C:2]2[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=2)([OH:24])[CH2:20][CH2:19]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 77304-BromoanisoleHCID 192201-Benzyl-4-piperidoneHCID 5462224Magnesium

Product 1

HCID 159073291-Benzyl-4-(4-methoxyphenyl)piperidin-4-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

4-Bromoanisole (13 ml, 0.1038 mol) in THF (13.5 ml) is added to a mixture of magnesium (2.24 g, 92.2 mmol) in dry THF (20 ml). When the magnesium is consumed the reagent mixture (XIII) is cooled in a ice/water bath and a mixture of 1-benzyl-4-piperidone (XII, 15 ml, 80.9 mmol) in THF (35 ml) is added dropwise over 21 minutes. The bath is then removed and the mixture stirred for 27 minutes, then poured into saturated aqueous sodium bicarbonate. The mixture is extracted several times with ether and the combined organic extracts are dried over magnesium sulfate, concentrated and the resulting material chromatographed on silica gel eluting with methanol/dichloromethane (4/96) containing ammonium hydroxide (0.4%). Impure fractions are combined and rechromatographed as above to give 1-benzyl-4-(4-methoxyphenyl)piperidin-4-ol (XIV), NMR (CDCl3) 1.74, 2.14, 2.46, 2.78, 3.58, 3.80, 6.88, 7.31 and 7.44 δ.

Workup

  1. customWhen the magnesium is consumed the reagent mixture (XIII)
  2. temperatureis cooled in a ice/water bath
  3. additionis added dropwise over 21 minutes
  4. customThe bath is then removed
  5. additionpoured into saturated aqueous sodium bicarbonate
  6. extractionThe mixture is extracted several times with ether
  7. dry with materialthe combined organic extracts are dried over magnesium sulfate
  8. concentrationconcentrated
  9. customthe resulting material chromatographed on silica gel eluting with methanol/dichloromethane (4/96)
  10. additioncontaining ammonium hydroxide (0.4%)
  11. customrechromatographed as above

Sources & evidence

ORD record
ord-e9815747569f4ede9aa26e49515a0e41
Source dataset
uspto-grants-1999_03
Patent number
US05877317

Reaction notes

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