Potassium Hydroxide → HCID 67440892, compound

HRID 2045327Notes

Reaction equation

HRID 2045327 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]I>[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

8

Reactant 5

HCID 14797Potassium HydroxideHCID 25517Ammonium ChlorideHCID 780131-IsopropylpiperazineHCID 145742L-ProlineHCID 67441305HCID 67441305, compound

Product 1

HCID 67440892HCID 67440892, compoundYield 99.2%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

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) iodide (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

  1. extractionextracted with ether (100 mL)
  2. customAfter removal of solvent
  3. 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-d478e60477674b9c8a48a5d1096e3be2
Source dataset
uspto-grants-2013_11
Patent number
US08586747B2

Reaction notes

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