1-Benzyl-4-piperidone → HCID 57459630, compound

HRID 1428510Notes

Reaction equation

HRID 1428510 reaction equation
[Li]CCCC.Br[C:7]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:8]=1[C:9]([OH:12])([CH3:11])[CH3:10].[CH2:18]([N:25]1[CH2:30][CH2:29][C:28](=[O:31])[CH2:27][CH2:26]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[NH4+].[Cl-]>C1COCC1>[CH2:18]([N:25]1[CH2:30][CH2:29][C:28]([C:7]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:8]=2[C:9]([OH:12])([CH3:11])[CH3:10])([OH:31])[CH2:27][CH2:26]1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

6

Reactant 4

HCID 192201-Benzyl-4-piperidoneHCID 25517Ammonium ChlorideHCID 68108625HCID 68108625, compoundHCID 178418339Butyllithium

Product 1

HCID 57459630HCID 57459630, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

To an anhydrous THF (50 mL) cooled at −70° C. stirred under nitrogen a 2.5 M solution of n-BuLi (4.22 mL, 10.54 mmol) was added. Then 2-bromo-5-fluoro-α,α-dimethyl-benzylalcohol (1.17 g, 5.02 mmol) [C.A.S.853271-16-6] was added dropwise. The resulting mixture was stirred at −70° C. for 2 h. Then a solution of 1-benzylpiperidin-4-one (1.33 g, 7.028 mmol) in anhydrous THF (10 ml) was added dropwise. Then, the resulting solution was stirred at r.t. overnight. The reaction mixture was poured into NH4Cl (aqueous sat. solution) at 5-10° C. The resulting aqueous solution was extracted with DCM. The organic layer was separated and concentrated in vacuo. The residue was purified by column chromatography (silica gel; heptane/EtOAc from 100/0 to 60/40 as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate D83 (0.4 g, 23%).

Workup

  1. additionwas added
  2. stirringThen, the resulting solution was stirred at r.t. overnight
  3. extractionThe resulting aqueous solution was extracted with DCM
  4. customThe organic layer was separated
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (silica gel; heptane/EtOAc from 100/0 to 60/40 as eluent)
  7. customThe desired fractions were collected
  8. concentrationconcentrated in vacuo
  9. customto yield intermediate D83 (0.4 g, 23%)

Sources & evidence

ORD record
ord-9a2b649554df43cfbdfac1d6a8e50c8f
Source dataset
uspto-grants-2015_01
Patent number
US08937060B2

Reaction notes

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