2-Piperidone → 1-(4-Bromo-5,7-difluoro-3-methylquinolin-2-yl)piperidin-2-one

HRID 1431606Notes

Reaction equation

HRID 1431606 reaction equation
Br[C:2]1[C:11]([CH3:12])=[C:10]([Br:13])[C:9]2[C:4](=[CH:5][C:6]([F:15])=[CH:7][C:8]=2[F:14])[N:3]=1.[NH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][C:17]1=[O:22].CN[C@H]1CCCC[C@@H]1NC.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.[Cu]I>[Br:13][C:10]1[C:9]2[C:4](=[CH:5][C:6]([F:15])=[CH:7][C:8]=2[F:14])[N:3]=[C:2]([N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][C:17]2=[O:22])[C:11]=1[CH3:12]

Participants

8

Reactant 4

HCID 126652-PiperidoneHCID 62657Potassium Phosphate, TribasicHCID 13822957(1S,2S)-(+)-N,N'-Dimethylcyclohexane-1,2-diamineHCID 596311142,4-Dibromo-5,7-difluoro-3-methylquinoline

Product 1

HCID 596310611-(4-Bromo-5,7-difluoro-3-methylquinolin-2-yl)piperidin-2-one

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

The 2,4-dibromo-5,7-difluoro-3-methylquinoline (2.00 g, 5.90 mmol), piperidin-2-one (590 mg, 5.90 mmol), copper (I) iodide (57.0 mg, 0.300 mmol), (1S,2S)—N1,N2-dimethylcyclohexane-1,2-diamine (0.094 mL, 0.59 mmol) and potassium phosphate tribasic (2.50 g, 12.0 mmol) were combined in 1,4-dioxane (10 mL) and stirred in the microwave reactor for 3.5 h. The reaction was diluted with water and extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine and dried over magnesium sulfate. The crude product was then purified by medium pressure chromatography (silica gel, 0 to 100% EtOAc: hexanes) to give 1-(4-bromo-5,7-difluoro-3-methylquinolin-2-yl)piperidin-2-one. Mass Spectrum (ESI) m/e=355.1 (M+1).

Workup

  1. extractionextracted with EtOAc (2×100 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. customThe crude product was then purified by medium pressure chromatography (silica gel, 0 to 100% EtOAc: hexanes)

Sources & evidence

ORD record
ord-b3401476a4c84d07816b1d1019276c9b
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

Loading…