Benzyl Bromide → (3RS,4RS)-1-benzyl-4-(4-fluoro-phenyl)-piperidin-3-ol

HRID 1858562Notes

Reaction equation

HRID 1858562 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH:9]2[OH:14])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH2:21](Br)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C(O)C>[CH2:21]([N:11]1[CH2:12][CH2:13][CH:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[CH:9]([OH:14])[CH2:10]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 10340Sodium CarbonateHCID 221266524-(4-Fluorophenyl)piperidin-3-ol

Product 1

HCID 22126857(3RS,4RS)-1-benzyl-4-(4-fluoro-phenyl)-piperidin-3-olYield 74.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A solution of 4.00 g (20.5 mmol) of (3RS,4RS)-4-(4-fluorophenyl)-piperidin-3-ol in 150 ml of ethanol was treated with 2.80 g (26.4 mmol) of sodium carbonate and refluxed. A solution of 2.50 ml (21.1 mmol) of benzyl bromide in 50 ml of ethanol was added dropwise within one hour and thereafter the mixture was held at reflux temperature for 2 hours. The pale brownish suspension was filtered and the filtrate was concentrated under reduced pressure. Subsequently, the residue was partitioned between methylene chloride and water, the organic phase was dried over magnesium sulphate and finally the solvent was distilled off under reduced pressure. The crude product was chromatographed on silica gel using a 2:3 mixture of ethyl acetate and hexane as the eluent. There were obtained 4.34 g (74% of theory) of (3RS,4RS)-1-benzyl-4-(4-fluoro-phenyl)-piperidin-3-ol as a colourless solid; MS: 285 (M)+.

Workup

  1. temperaturerefluxed
  2. temperatureat reflux temperature for 2 hours
  3. filtrationThe pale brownish suspension was filtered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customSubsequently, the residue was partitioned between methylene chloride and water
  6. dry with materialthe organic phase was dried over magnesium sulphate
  7. distillationfinally the solvent was distilled off under reduced pressure
  8. customThe crude product was chromatographed on silica gel using
  9. additiona 2:3 mixture of ethyl acetate and hexane as the eluent

Sources & evidence

ORD record
ord-db821e7c098d42c38f8266940d62a80b
Source dataset
uspto-grants-2000_11
Patent number
US06150526

Reaction notes

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