Potassium Hydroxide → HCID 67440892, compound

HRID 1801048Notes

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].[CH:25]([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)([CH3:27])[CH3:26].N1CCC[C@H:35]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:31]3[CH2:32][CH2:33][N:28]([CH:25]([CH3:27])[CH3:26])[CH2:29][CH2:30]3)[CH:18]=[C:19]([F:21])[CH:20]=1)[C:9]([CH3:24])([CH3:23])[CH2:8]2)=[O:4])[CH3:35]

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), 1-isopropyl piperazine (0.64 g, 5.0 mmol), copper (I) iodidie (120 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) (40% ethyl acetate/hexanes) to afford 2-[3-fluoro-5-(4-isopropyl-piperazin-1-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester (0.27 g, 60%) as a white solid: LC/MS m/e calcd for C27H36FN3O2 (M+H)+: 454.6, observed: 454.3.

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) (40% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-ce7c9cad240746768c51952252f5b845
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08344137B2

Reaction notes

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