2-Pyrrolidone → HCID 67441184, compound

HRID 2045330Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]([C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[C:17](Br)[CH:16]=1)[C:9]([CH3:24])([CH3:23])[CH2:8]2)=[O:4].[NH:25]1[CH2:29][CH2:28][CH2:27][C:26]1=[O:30].N1CCC[C@H:32]1C(O)=O.[OH-].[K+].[Cl-].[NH4+]>CS(C)=O.[Cu+]>[CH2:1]([O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]([C:15]1[CH:16]=[C:17]([N:25]3[CH2:29][CH2:28][CH2:27][C:26]3=[O:30])[CH:18]=[C:19]([F:21])[CH:20]=1)[C:9]([CH3:24])([CH3:23])[CH2:8]2)=[O:4])[CH3:32]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 2-(3-bromo-5-fluoro-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid methyl ester (0.41 g, 1.0 mmol), pyrrolidin-2-one (0.24 g, 3.0 mmol), copper (I) iodidie (110 mg, 0.6 mmol), L-proline (69 mg, 0.6 mmol) and potassium hydroxide (33.6 mg, 0.6 mmol) in DMSO (2 mL) was stirred at 120° C. for 2 hours. Then treated with saturated ammonium chloride (20 mL), extracted with ether (100 mL). After removal of solvent, the residue was purified on flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company)(20% ethyl acetate/hexanes) to afford 2-[3-fluoro-5-(2-oxo-pyrrolidin-1-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester (0.25 g, 61%) as a white solid: LC/MS m/e calcd for C24H27FN2O3 (M+H)+: 411.5, observed: 411.3.

Workup

extractionextracted with ether (100 mL)
customAfter removal of solvent
customthe residue was purified on flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company)(20% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-db6b9caa409b47229854a32c3b673610
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08586747B2

Reaction notes

Loading…