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

HRID 1507239Notes

Reaction equation

HRID 1507239 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.[CH2:10]([N:17]1[CH2:22][CH2:21][C:20](=[O:23])[CH2:19][CH2:18]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>C1COCC1>[CH2:10]([N:17]1[CH2:22][CH2:21][C:20]([C:2]2[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=2)([OH:23])[CH2:19][CH2:18]1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

4

Reactant 2

HCID 77304-BromoanisoleHCID 192201-Benzyl-4-piperidone

Product 1

HCID 159073291-Benzyl-4-(4-methoxyphenyl)piperidin-4-olYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-bromo-4-methoxybenzene (5 g, 27 mmol) in THF (100 mL) at −78° C. was added a solution of 1.6 M N-butyl lithium/hexanes (18.4 mL, 29.4 mmol), and the reaction mixture was stirred for 1 hr. Then a solution of 1-benzylpiperidin-4-one (4.81 g, 25.4 mmol) in 50 mL of THF was added. After the addition, the mixture was allowed to warm up to rt and was stirred for 1 h. The reaction was then quenched by the addition of 100 mL of 1.5 M aqueous HCl and the mixture was extracted with 200 mL of ethyl acetate. The organic layer was dried over Na2SO4, filtered, and concentrated under vacuum to yield 7.1 g (72% yield) of 1-benzyl-4-(4-methoxyphenyl)piperidin-4-ol. LCMS (method F) RT 2.19 min, 81% AP, m/z298.4 (M+H+), 1H NMR (300 MHz, DMSO-d6) δ 7.23-7.39 (m 8.5H), 6.94 (m, 0.5H), 6.84-6.94 (m, 2H), 4.66 (s, 1H), 3.74 (s, 0.8H), 3.72 (s, 3H), 3.32 (s, 2H), 2.50-2.67 (m, 2H), 2.34-2.45 (m, 3H), 1.83-1.90 (m, 2H), 1.55 (d, J=11, 2H).

Workup

  1. additionAfter the addition
  2. stirringwas stirred for 1 h
  3. customThe reaction was then quenched by the addition of 100 mL of 1.5 M aqueous HCl
  4. extractionthe mixture was extracted with 200 mL of ethyl acetate
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-7f88ef58b7a142a0a38031160f0ec27f
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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