1-Acetyl-4-benzoylpiperidine → HCID 118005587, compound

HRID 1478517Notes

Reaction equation

HRID 1478517 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[C:9]2[C:14](=[C:15]([CH3:17])[CH:16]=1)[N:13]=[C:12]([Cl:18])[C:11]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[C:10]2[Cl:25].[C:26]([CH:34]1[CH2:39][CH2:38][N:37]([C:40](=[O:42])[CH3:41])[CH2:36][CH2:35]1)(=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C1COCC1>[Cl:18][C:12]1[C:11]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:10]([Cl:25])[C:9]2[C:14](=[C:15]([CH3:17])[CH:16]=[C:7]([C:26]([OH:33])([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:34]3[CH2:39][CH2:38][N:37]([C:40](=[O:42])[CH3:41])[CH2:36][CH2:35]3)[CH:8]=2)[N:13]=1

Participants

5

Reactant 3

HCID 27407141-Acetyl-4-benzoylpiperidine2×HCID 86716089HCID 86716089, compound2×HCID 178418339Butyllithium

Product 1

HCID 118005587HCID 118005587, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of n-butyllithium (1.6 M in hexanes, 0.5 mL, 0.8 mmol) was added dropwise by syringe to a solution of 6-bromo-2,4-dichloro-8-methyl-3-phenylquinoline (0.32 g, 0.88 mmol, Intermediate 3) in dry deoxygenated THF (10 mL) at −78° C. After 2 minutes, a solution of 1-(4-benzoylpiperidin-1-yl)ethanone (0.203 g, 0.88 mmol, Intermediate 4) in dry THF (4 mL) was added dropwise by syringe. An additional 2 mL of THF was used to complete the quantitative addition. After 10 minutes, the flask was removed from the dry-ice bath and placed into an ice-water bath. After 1 hour, the reaction was quenched with saturated aqueous ammonium chloride solution and the mixture was partitioned between water and EtOAc. The layers were separated and the aqueous phase was further extracted with EtOAc and washed with saturated aqueous NaCl solution. The organic phase was dried (MgSO4), filtered, and concentrated to dryness. The crude product was purified by flash column chromatography (silica gel, 0-100% EtOAc-DCM) to provide the title compound. MS m/e 519.1 (M+H)+.

Workup

  1. customin dry
  2. customdeoxygenated THF (10 mL) at −78° C
  3. additionthe quantitative addition
  4. waitAfter 10 minutes
  5. customthe flask was removed from the dry-ice bath
  6. customplaced into an ice-water bath
  7. waitAfter 1 hour
  8. customthe reaction was quenched with saturated aqueous ammonium chloride solution
  9. customthe mixture was partitioned between water and EtOAc
  10. customThe layers were separated
  11. extractionthe aqueous phase was further extracted with EtOAc
  12. washwashed with saturated aqueous NaCl solution
  13. dry with materialThe organic phase was dried (MgSO4)
  14. filtrationfiltered
  15. concentrationconcentrated to dryness
  16. customThe crude product was purified by flash column chromatography (silica gel, 0-100% EtOAc-DCM)

Sources & evidence

ORD record
ord-badc31c0d49d4f9c89530578387ede15
Source dataset
uspto-grants-2016_08
Patent number
US09403816B2

Reaction notes

Loading…