1-Benzyl-4-piperidone → 1-Benzyl-4-hydroxy-4-(6-methoxynaphth-2-yl)piperidine

HRID 380544Notes

Reaction equation

HRID 380544 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[CH:8][CH:7]=[C:6]2Br.C([Li])(C)(C)C.[CH2:19]([N:26]1[CH2:31][CH2:30][C:29](=[O:32])[CH2:28][CH2:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>O1CCCC1>[CH2:19]([N:26]1[CH2:31][CH2:30][C:29]([OH:32])([C:8]2[CH:7]=[CH:6][C:5]3[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=3)[CH:9]=2)[CH2:28][CH2:27]1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 192201-Benzyl-4-piperidoneHCID 130258361-bromo-7-methoxyNaphthaleneHCID 178418306HCID 178418306, compound

Product 1

HCID 183652491-Benzyl-4-hydroxy-4-(6-methoxynaphth-2-yl)piperidineYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 5.0 gm (21.1 mMol) 6-methoxy-4-bromonaphthalene in 120 mL tetrahydrofuran was first cooled to −78° C. and then 27.3 mL (46.4 mMol) tert-butyllithium (1.7 M in pentane) were added and the resulting solution stirred for about 1.5 hours. At this point a solution of 4.1 mL (22.1 mMol) 1-benzylpiperidin-4-one in 30 mL tetrahydrofuran was added and the reaction mixture was allowed to warm gradually to room temperature. After 3 hours the reaction was quenched by the addition of 2 N sodium hydroxide. The resulting mixture was extracted with diethyl ether. The organic extracts were combined, washed with saturated aqueous sodium chloride, and concentrated under reduced pressure. The residue was subjected to flash silica gel chromatography, eluting with dichloromethane containing from 0 to 2% methanol. Fractions containing product were combined and concentrated under reduced pressure. The residue was crystallized from ethyl acetate to provide 4.62 gm (63%) of the desired compound as a white solid.

Workup

  1. customAfter 3 hours the reaction was quenched by the addition of 2 N sodium hydroxide
  2. extractionThe resulting mixture was extracted with diethyl ether
  3. washwashed with saturated aqueous sodium chloride
  4. concentrationconcentrated under reduced pressure
  5. washeluting with dichloromethane containing from 0 to 2% methanol
  6. additionFractions containing product
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was crystallized from ethyl acetate

Sources & evidence

ORD record
ord-73fd92d80172435da08ae102ff585a18
Source dataset
uspto-grants-2001_10
Patent number
US06303627B1

Reaction notes

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