Ethyl Acetate → HCID 70496068, compound

HRID 2408091Notes

Reaction equation

HRID 2408091 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([F:24])[CH:8]=[C:9]2[C:14]=1[NH:13][CH:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17](Br)[CH:16]=1)[CH2:11][C:10]2([CH3:23])[CH3:22])=[O:4].[F:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([F:24])[CH:8]=[C:9]2[C:14]=1[NH:13][CH:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N:35]3[CH2:34][CH2:33][N:32]([C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=4[F:25])[CH2:37][CH2:36]3)[CH:16]=1)[CH2:11][C:10]2([CH3:23])[CH3:22])=[O:4]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 705291-(2-Fluorophenyl)piperazineHCID 70496195HCID 70496195, compound

Product 1

HCID 70496068HCID 70496068, compoundYield 61%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-(3-bromo-phenyl)-6-fluoro-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester (392 mg, 1.0 mmol), 1-(2-fluorophenyl)-piperazine (216 mg, 1.2 mmol), palladium (II) acetate (11.2 mg, 0.05 mmol), xantphos (34.7 mg, 0.06 mmol) and cesium carbonate (652 mg, 2 mmol) in toluene (5 mL) was heated for 3 h at 120° C. After colling to room temperature, the mixture was treated with ethyl acetate (50 mL) and washed with water (20 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. Purification on flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company) (50% ethyl acetate/hexanes) to afford 6-fluoro-2-{3-[4-(2-fluoro-phenyl)-piperazin-1-yl]-phenyl}-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester (0.3 g, 60%) as a white solid: MS (ESI) M+1=492.1.

Workup

  1. customAfter colling to room temperature
  2. washwashed with water (20 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customPurification on flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company) (50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-d5c72cee73a14e96ae25f82d4f8bf2a0
Source dataset
uspto-grants-2014_08
Patent number
US08809369B2

Reaction notes

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