tert-Butyl 4-oxopiperidine-1-carboxylate → HCID 21268335, compound

HRID 1457002Notes

Reaction equation

HRID 1457002 reaction equation
C([Li])CCC.Br[C:7]1[C:11]2[CH:12]=[C:13]([Cl:16])[CH:14]=[CH:15][C:10]=2[S:9][CH:8]=1.[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18]>C(OCC)C>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]2[S:9][CH:8]=[C:7]([C:27]3([OH:30])[CH2:26][CH2:25][N:24]([C:22]([O:21][C:17]([CH3:19])([CH3:18])[CH3:20])=[O:23])[CH2:29][CH2:28]3)[C:11]=2[CH:12]=1

Participants

5

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 142423383-Bromo-5-chlorobenzo[b]thiopheneHCID 178418339Butyllithium

Product 1

HCID 21268335HCID 21268335, compoundYield 58.4%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of 1.55 mL (1.86 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 0.418 gm (1.68 mMol) 3-bromo-5-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 0.401 gm (2.0 mMol) 1-tert-butoxycarbonyl-4-piperidone in 5.0 mL diethyl ether. The reaction was stirred an additional 2 hours at -78° C. and was then gradually 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 0.36 gm (58.4%) of the desired compound as a colorless foam.

Workup

  1. stirringThe reaction was stirred an additional 2 hours at -78° C.
  2. temperaturewas then gradually 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-8bdea7f536a84fc8bf604a0dce5b4e09
Source dataset
uspto-grants-1998_12
Patent number
US05846982

Reaction notes

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