Piperazine → HCID 67442567, compound

HRID 1801040Notes

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[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.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[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)[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), piperazine (0.26 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) (40% ethyl acetate/hexanes) to afford 2-(3-fluoro-5-piperazin-1-yl-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester (0.18 g, 43%) as a white solid: LC/MS m/e calcd for C24H30FN3O2 (M+H)+: 412.5, observed: 412.3.

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-5135916e9a6a4788afc40258871f05ca
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08344137B2

Reaction notes

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