1,3-Dibromo-5,5-dimethylhydantoin → HCID 66831377, compound

HRID 405996Notes

Reaction equation

HRID 405996 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[C:18](=[O:19])[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([F:20])[CH:16]=3)[N:11]([CH3:21])[C:10]=2[CH2:22][CH3:23])[CH:5]=[C:6]([F:8])[CH:7]=1.[Br:24]N1C(C)(C)C(=O)N(Br)C1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)(Cl)Cl>[Br:24][CH:22]([C:10]1[N:11]([CH3:21])[C:12]2[C:17]([C:18](=[O:19])[C:9]=1[C:4]1[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([F:1])[CH:3]=1)=[CH:16][C:15]([F:20])=[CH:14][CH:13]=2)[CH3:23]

Participants

6

Reactant 4

HCID 64791,3-Dibromo-5,5-dimethylhydantoinHCID 7187Benzoyl PeroxideHCID 516892Sodium BicarbonateHCID 66831368HCID 66831368, compound

Product 1

HCID 66831377HCID 66831377, compound

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Procedure

3-(3,5-Difluorophenyl)-2-ethyl-6-fluoro-1-methylquinolin-4(1H)-one (120 mg, 0.38 mmol) and 1,3-dibromo-5,5-dimethylhydantoin (76 mg, 0.7 eq) were suspended in carbon tetrachloride (5 mL). To the mixture was added benzoyl peroxide (9.2 mg, 0.1 eq) and the mixture was heated at reflux for 3 h. After cooling to rt, satd. aq sodium bicarbonate solution (5 mL) was added. The layers were separated and the aq layer was extracted with DCM (3 mL×2). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concd under reduced pressure to give 2-(1-bromoethyl)-3-(3,5-difluorophenyl)-6-fluoro-1-methylquinolin-4(1H)-one as a yellow solid. Mass Spectrum (ESI) m/e=397 (M+1). The yellow solid was dissolved in DMF (5 mL) and treated with phthalimide potassium salt (140 mg, 2.0 eq) at 60° C. for 4 h. The reaction mixture was partitioned between water and EtOAc, The layers were separated and the aq layer was extracted with EtOAc (10 mL×2). The combined organic layers were washed with water (10 mL×2), brine (10 mL), dried over Na2SO4, filtered, and concd under reduced pressure. The residue was purified by combiflash on silica gel (DCM/hexane, 0/1 to 1/1) to give 2-(1-(3-(3,5-difluorophenyl)-6-fluoro-1-methyl-4-oxo-1,4-dihydroquinolin-2-yl)ethyl)isoindoline-1,3-dione as a white solid. Mass Spectrum (ESI) m/e=463 (M+1).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 3 h
  3. customThe layers were separated
  4. extractionthe aq layer was extracted with DCM (3 mL×2)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered

Sources & evidence

ORD record
ord-b5bd12e006694254bade0904f2d49020
Source dataset
uspto-grants-2014_06
Patent number
US08754089B2

Reaction notes

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