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

HRID 2111602Notes

Reaction equation

HRID 2111602 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.C([Li])CCC.[CH2:15]([N:22]1[CH2:27][CH2:26][C:25](=[O:28])[CH2:24][CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[NH4+].[Cl-]>C1COCC1.CCCCCC>[CH2:15]([N:22]1[CH2:27][CH2:26][C:25]([C:2]2[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=2)([OH:28])[CH2:24][CH2:23]1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

7

Reactant 4

HCID 77304-BromoanisoleHCID 192201-Benzyl-4-piperidoneHCID 25517Ammonium ChlorideHCID 178418339Butyllithium

Product 1

HCID 159073291-Benzyl-4-(4-methoxyphenyl)piperidin-4-olYield 68.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 44.8 g of 1-bromo-4-methoxybenzene in 700 ml of THF is cooled to −78° C., 168 ml of a 1.6M solution of n-butyllithium in hexane are added dropwise and the mixture is then stirred at −78° C. for 30 minutes. The solution of 45.3 g of 1-benzyl-4-piperidinone in 100 ml of THF is then added dropwise and the mixture is stirred at −78° C. for 2 hours. The reaction mixture is poured into 400 ml of saturated NH4Cl solution and extracted with ether, the organic phase is washed with water, with saturated NaCl solution and dried over MgSO4, and the solvent is evaporated off under vacuum. 48.6 g of the expected product are obtained after crystallization from hexane.

Workup

  1. stirringthe mixture is stirred at −78° C. for 2 hours
  2. extractionextracted with ether
  3. washthe organic phase is washed with water, with saturated NaCl solution
  4. dry with materialdried over MgSO4
  5. customthe solvent is evaporated off under vacuum

Sources & evidence

ORD record
ord-a34ac7fb7d234edf800463cc3dfa87d4
Source dataset
uspto-grants-2009_04
Patent number
US07521449B2

Reaction notes

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