1-Methyl-4-piperidone → HCID 18797328, compound

HRID 1003590Notes

Reaction equation

HRID 1003590 reaction equation
C([Li])CCC.Br[C:7]1[C:11]2[CH:12]=[CH:13][C:14]([Cl:16])=[CH:15][C:10]=2[S:9][CH:8]=1.[CH3:17][N:18]1[CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]1>C(OCC)C>[Cl:16][C:14]1[CH:13]=[CH:12][C:11]2[C:7]([C:21]3([OH:24])[CH2:22][CH2:23][N:18]([CH3:17])[CH2:19][CH2:20]3)=[CH:8][S:9][C:10]=2[CH:15]=1

Participants

5

Reactant 3

HCID 740491-Methyl-4-piperidoneHCID 12398619HCID 12398619, compoundHCID 178418339Butyllithium

Product 1

HCID 18797328HCID 18797328, compoundYield 27.9%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 0.82 mL (0.98 mMol) n-butyllithium in 5.0 mL diethyl ether was cooled to -78° C. under a nitrogen atmosphere. To this cooled solution was added a solution of 0.22 gm (0.89 mMol) 3-bromo-6-chlorobenzothiophene in 10.0 mL diethyl ether. The reaction mixture was stirred at -78° C. for 1 hour and then to it was added dropwise a solution of 0.12 mL (0.98 mMol) 1-methyl-4-piperidone in 5.0 mL and the reaction was stirred an additional 2 hours at -78° C., then was warmed to -20° C. over 55 minutes. The reaction mixture was then quenched with saturated aqueous sodium bicarbonate, diluted with additional diethyl ether and the phases separated. The organic phase was washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to flash silica chromatography, eluting with toluene containing 10% ethyl acetate. Fractions shown to contain product were combined and concentrated under reduced pressure to give 0.07 gm (25%) of the title compound as a colorless solid.

Workup

  1. stirringthe reaction was stirred an additional 2 hours at -78° C.
  2. temperaturewas warmed to -20° C. over 55 minutes
  3. customThe reaction mixture was then quenched with saturated aqueous sodium bicarbonate
  4. additiondiluted with additional diethyl ether
  5. customthe phases separated
  6. washThe organic phase was washed with saturated aqueous sodium chloride
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. washeluting with toluene containing 10% ethyl acetate
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7835caea9e494a9e83d304b3572bb54a
Source dataset
uspto-grants-2000_04
Patent number
US06046215

Reaction notes

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