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

HRID 1618680Notes

Reaction equation

HRID 1618680 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

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, 11.9 mmol) were combined in 1,4-dioxane (10 mL) and stirred in a 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 MgSO4. The crude product was then purified by column 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=355.0 [(M+1) (79Br)] and 357.1 [(M+1) (81Br)].

Workup

  1. extractionextracted with EtOAc (2×100 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. customThe crude product was then purified by column chromatography (silica gel, 0 to 100% EtOAc:hexanes)

Sources & evidence

ORD record
ord-700030f9031640b59346c04c97a4890c
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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