2-Bromoanisole → 2-(1-Benzylpiperidin-4-yl)-1-(2-methoxyphenyl)ethanol

HRID 914806Notes

Reaction equation

HRID 914806 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH3:9].[CH2:10]([N:17]1[CH2:22][CH2:21][CH:20]([CH2:23][CH:24]=[O:25])[CH2:19][CH2:18]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Cl-].[NH4+]>O1CCCC1.C([Li])CCC>[CH2:10]([N:17]1[CH2:22][CH2:21][CH:20]([CH2:23][CH:24]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[O:8][CH3:9])[OH:25])[CH2:19][CH2:18]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 3

HCID 113582-BromoanisoleHCID 25517Ammonium ChlorideHCID 100136024-Piperidineacetaldehyde, 1-(phenylmethyl)-

Product 1

HCID 222484442-(1-Benzylpiperidin-4-yl)-1-(2-methoxyphenyl)ethanolYield 69%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 178418339ButyllithiumSolvent

Procedure

After dissolving 2.04 g of 2-bromoanisole in 22 ml of tetrahydrofuran, 3.6 ml of n-butyllithium (2.66 M, n-hexane solution) was added dropwise while stirring at below −60° C., and after 30 minutes, a solution of 1.58 g of 1-benzylpiperidine-4-acetaldehyde in tetrahydrofuran (5 ml) was added and stirring was continued for 30 minutes. Saturated aqueous ammonium chloride solution was added, the temperature was raised to room temperature, and extraction was performed with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by NH silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (1.63 g, 69% yield).

Workup

  1. additionwas added dropwise
  2. stirringstirring
  3. waitwas continued for 30 minutes
  4. extractionextraction
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. customThe residue was purified by NH silica gel column chromatography (solvent: n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-ea8f0df13c44464792d51d2a7324e826
Source dataset
uspto-grants-2007_09
Patent number
US07265108B2

Reaction notes

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