Cesium carbonate → HCID 70496746, compound

HRID 2408087Notes

Reaction equation

HRID 2408087 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].Cl.[C:26]1([CH3:38])[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.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.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C>[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[CH2:36][CH2:37][N:32]([C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=4[CH3:38])[CH2:33][CH2:34]3)[CH:16]=1)[CH2:11][C:10]2([CH3:23])[CH3:22])=[O:4]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 122278951-(o-Tolyl)piperazine HydrochlorideHCID 70496195HCID 70496195, compound

Product 1

HCID 70496746HCID 70496746, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

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 (3.0 g, 7.65 mmol), 1-o-tolyl-piperazine hydrochloride (1.95 g, 9.2 mmol), palladium (II) acetate (172 mg, 0.77 mmol), xantphos (266 mg, 0.46 mmol) and cesium carbonate (5.0 g, 15.3 mmol) in toluene (20 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-4,4-dimethyl-2-[3-(4-o-tolyl-piperazin-1-yl)-phenyl]-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester (2.2 g, 60%) as a white solid: MS (ESI) M+1=488.4.

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-e9dcf4a1d1634e5995b2bab2b24dd918
Source dataset
uspto-grants-2014_08
Patent number
US08809369B2

Reaction notes

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