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

HRID 1618695Notes

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[CH2:20][CH2:19][CH2:18][C:17]1=[O:21].CN[C@H]1CCCC[C@@H]1NC.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.[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[CH2:20][CH2:19][CH2:18][C:17]2=[O:21])[C:11]=1[CH3:12]

Participants

Conditions

Temperature: 110 °C

Procedure

2,4-Dibromo-5,7-difluoro-3-methylquinoline (500 mg, 1.50 mmol), pyrrolidin-2-one (0.110 mL, 1.50 mmol), copper (I) iodide (14 mg, 0.074 mmol), (1S,2S)—N1,N2-dimethylcyclohexane-1,2-diamine (0.023 mL, 0.150 mmol) and potassium phosphate tribasic (630 mg, 3.00 mmol) were slurried in 1,4-dioxane (5 mL) and stirred in a microwave reactor at 110° C. for 2 h. The resulting slurry was partitioned between EtOAc and water. The separated aqueous layer was extracted with EtOAc and the combined organic extracts were washed with brine (1×50 mL) and dried over MgSO4. The crude product was purified by column chromatography (silica gel, 0 to 100% EtOAc:DCM) to give 1-(4-bromo-5,7-difluoro-3-methylquinolin-2-yl)pyrrolidin-2-one. Mass Spectrum (ESI) m/e=341.0 [(M+1) (79Br)] and 343.1 [(M+1) (81Br)].

Workup

customThe resulting slurry was partitioned between EtOAc and water
extractionThe separated aqueous layer was extracted with EtOAc
washthe combined organic extracts were washed with brine (1×50 mL)
dry with materialdried over MgSO4
customThe crude product was purified by column chromatography (silica gel, 0 to 100% EtOAc:DCM)

Sources & evidence

ORD record: ord-cbbaae93c801485488f54cdec3658776
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765940B2

Reaction notes

Loading…