1,2-Dibromoethane → 1-Benzyl-4-(4-fluoro-benzyl)-piperidin-4-ol

HRID 854604Notes

Reaction equation

HRID 854604 reaction equation
[Mg].BrCCBr.Cl[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=1.[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.[Cl-].[NH4+]>C1COCC1.O>[CH2:15]([N:22]1[CH2:27][CH2:26][C:25]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)([OH:28])[CH2:24][CH2:23]1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

8

Reactant 5

HCID 78391,2-DibromoethaneHCID 96024-Fluorobenzyl chlorideHCID 192201-Benzyl-4-piperidoneHCID 25517Ammonium ChlorideHCID 5462224Magnesium

Product 1

HCID 108280121-Benzyl-4-(4-fluoro-benzyl)-piperidin-4-ol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of magnesium metal (4.15 g, 170.5 mmol) in anhydrous THF (40 ml) is added 1,2-dibromoethane (1.53 g, 8.12 mmol) and the mixture warmed gently. To the reaction mixture is added a solution of 1-chloromethyl-4-fluoro-benzene (23.5 g, 162.4 mmol) in THF (20 ml) dropwise over 1.5 hours. The reaction mixture is cooled to RT and stirred for 0.5 hours followed by cooling to −10° C. and addition of a solution of 1-benzyl-piperidin-4-one (9.19 g, 48.6 mmol) in THF (20 ml) dropwise over 0.5 hours. During the addition the reaction temperature is maintained below 0° C. After addition is complete the reaction is allowed to reach RT and stirred for 4 days. The resultant suspension is cooled in ice, treated with saturated ammonium chloride, stirred for 0.3 hours, treated with water and the mixture extracted with ethyl acetate. The ethyl acetate is dried with magnesium sulphate and evaporated. The crude product is purified by flash silica chromatography (methanol:dichloromethane: anmuoniumhydroxide, 1:100:0.5 elution) to afford 1-benzyl-4-(4-fluoro-benzyl)-piperidin-4-ol [MH]+ 300.8

Workup

  1. temperaturethe mixture warmed gently
  2. temperatureby cooling to −10° C.
  3. additionDuring the addition the reaction temperature
  4. temperatureis maintained below 0° C
  5. additionAfter addition
  6. customto reach RT
  7. stirringstirred for 4 days
  8. stirringstirred for 0.3 hours
  9. extractionthe mixture extracted with ethyl acetate
  10. dry with materialThe ethyl acetate is dried with magnesium sulphate
  11. customevaporated
  12. customThe crude product is purified by flash silica chromatography (methanol:dichloromethane: anmuoniumhydroxide, 1:100:0.5 elution)

Sources & evidence

ORD record
ord-67c7081ecd15412484daacc162169f56
Source dataset
uspto-grants-2007_08
Patent number
US07259173B2

Reaction notes

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