1-Bromonaphthalene → 1-Benzyl-4-hydroxy-4-(naphth-1-yl)piperidine

HRID 1416194Notes

Reaction equation

HRID 1416194 reaction equation
C([Li])(CC)C.Br[C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9][CH:8]=1.[CH2:17]([N:24]1[CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>O1CCCC1>[CH2:17]([N:24]1[CH2:29][CH2:28][C:27]([OH:30])([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:10]=[CH:9][CH:8]=2)[CH2:26][CH2:25]1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 70011-BromonaphthaleneHCID 192201-Benzyl-4-piperidoneHCID 178418400CID 53628100

Product 1

HCID 183653421-Benzyl-4-hydroxy-4-(naphth-1-yl)piperidineYield 32.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 48.7 mL (63.3 mMol) sec-butyllithium (1.3 M in tetrahydrofuran) was added to a solution of 10.0 gm (42.2 mMol) 1-bromonaphthalene in 200 mL tetrahydrofuran at -78° C. The reaction mixture was stirred at that temperature for 1.5 hours and to it was then added a solution of 8.2 mL (44.3 mMol) 1-benzyl-4-piperidone in 40 mL tetrahydrofuran dropwise. The reaction mixture was allowed to warm to room temperature and was then quenched by the addition of 2N sodium hydroxide. The resulting mixture was extracted well with diethyl ether. The combined organic extracts were washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to flash silica gel chromatography, eluting with dichloromethane which contained 0-2% methanol. Fractions containing product were combined and concentrated under reduced pressure to provide 4.34 gm (32%) of the desired compound as a white foam.

Workup

  1. customwas then quenched by the addition of 2N sodium hydroxide
  2. extractionThe resulting mixture was extracted well with diethyl ether
  3. washThe combined organic extracts were washed with saturated aqueous sodium chloride
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. washeluting with dichloromethane which
  7. additionFractions containing product
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-638b1f2aebb14a058a6350a14fdb011e
Source dataset
uspto-grants-1999_06
Patent number
US05912256

Reaction notes

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