Diisopropylamine → HCID 57982420, compound

HRID 1868522Notes

Reaction equation

HRID 1868522 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]([O:23][Si](C)(C)C)C#N)=[C:16]([F:28])[CH:15]=1.[C:29]([N:32]1[CH2:37][CH2:36][C:35](=[O:38])[CH2:34][CH2:33]1)(=[O:31])[CH3:30]>C1COCC1>[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]([C:35]2([OH:38])[CH2:36][CH2:37][N:32]([C:29](=[O:31])[CH3:30])[CH2:33][CH2:34]2)=[O:23])=[C:16]([F:28])[CH:15]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 122563N-Acetyl-4-piperidoneHCID 57982305HCID 57982305, compoundHCID 178418339Butyllithium

Product 1

HCID 57982420HCID 57982420, compoundYield 42.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of diisopropylamine (4.42 mL, 31.59 mmol) in THF (20 mL) at 0° C. under Ar, was added n-BuLi (12.63 mL, 31.59 mmol, 2.5 M solution in hexane). The mixture was stirred at 0° C. for 30 min. After cooling to −78° C., (4-chloro-2-fluoro-phenyl)-trimethylsilanyloxyacetonitrile (8.12 g, 31.59 mmol) was added. After stirring at −78° C. for 1.5 h, 1-acetyl-piperidin-4-one (4.45 g, 31.59 mmol) was added. The final mixture was stirred at −20° C. for overnight. After concentration, EtOAc (100 mL) was added. The organic phase was washed with Sat. NH4OAc solution, Sat. NaHCO3 solution and concentrated. The residue was dissolved in MeOH (30 mL). 1N HCl solution (20 mL) was added. The mixture was stirred at RT for 2 h. After concentrating the mixture, EtOAc (50 mL) was added. The organic layer was basified with Sat. NaHCO3, dried over Na2SO4 and concentrated. The residue was purified by column chromatography (Ethyl acetate) to give the desired product (4 g, 42% yield) as a white solid. MS: (ESI), M/Z, 300 (M+1). Retention time: 0.87 min (FA-standard).

Workup

  1. temperatureAfter cooling to −78° C.
  2. stirringAfter stirring at −78° C. for 1.5 h
  3. concentrationAfter concentration, EtOAc (100 mL)
  4. additionwas added
  5. washThe organic phase was washed with Sat. NH4OAc solution, Sat. NaHCO3 solution
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in MeOH (30 mL)
  8. addition1N HCl solution (20 mL) was added
  9. stirringThe mixture was stirred at RT for 2 h
  10. concentrationAfter concentrating the mixture, EtOAc (50 mL)
  11. additionwas added
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated
  14. customThe residue was purified by column chromatography (Ethyl acetate)

Sources & evidence

ORD record
ord-92f3421467824d0088a2d5effc979078
Source dataset
uspto-grants-2009_12
Patent number
US07635698B2

Reaction notes

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