Potassium Carbonate → 6-Chloro-4-ethoxy-7-methoxy-2-methyl-3-(4-(4-(trifluoromethoxy)phenoxy)phenyl)quinoline

HRID 1500221Notes

Reaction equation

HRID 1500221 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]=[C:7]([CH3:14])[C:6](I)=[C:5]2[O:16][CH2:17][CH3:18].[F:19][C:20]([F:39])([F:38])[O:21][C:22]1[CH:37]=[CH:36][C:25]([O:26][C:27]2[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=2)=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]=[C:7]([CH3:14])[C:6]([C:30]1[CH:29]=[CH:28][C:27]([O:26][C:25]3[CH:36]=[CH:37][C:22]([O:21][C:20]([F:19])([F:38])[F:39])=[CH:23][CH:24]=3)=[CH:32][CH:31]=1)=[C:5]2[O:16][CH2:17][CH3:18]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 56776567{4-[4-(Trifluoromethoxy)phenoxy]phenyl}boronic acidHCID 670163176-Chloro-4-ethoxy-3-iodo-7-methoxy-2-methylquinoline

Product 1

HCID 670163156-Chloro-4-ethoxy-7-methoxy-2-methyl-3-(4-(4-(trifluoromethoxy)phenoxy)phenyl)quinolineYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 6-chloro-4-ethoxy-3-iodo-7-methoxy-2-methylquinoline (1.56 g, 4.13 mmol), (4-(4-(trifluoromethoxy)phenoxy) phenyl) boronic acid (1.85 g, 6.20 mmol) and palladium (0) tetrakis triphenylphosphine (239 mg, 0.207 mmol) in degassed dimethylformamide was added 8.25 ml of a 2 N aqueous potassium carbonate solution. The reaction mixture was stirred 18 hours at 85° C., filtered through celite and concentrated in vacuo. The resulting residue was resuspended in dichloromethane and water. The organic layer was extracted with brine, dried over magnesium sulfate and concentrated in vacuo. Purification by silica gel chromatography (0-20% ethyl acetate in dichloromethane) provided 1.18 g 6-chloro-4-ethoxy-7-methoxy-2-methyl-3-(4-(4-(trifluoromethoxy)phenoxy)phenyl)quinoline (57% yield) as a light brown solid. 1H NMR (400 MHz, CDCl3) δ 8.11 (s, 1H), 7.43 (s, 1H), 7.31-7.36 (m, 2H), 7.22-7.26 (m, 2H), 7.07-7.14 (m, 4H), 4.04 (s, 3H), 3.71 (q, J=7.1 Hz, 2H), 2.49 (s, 3H), 1.18 (t, J=7.1 Hz, 3H).

Workup

  1. filtrationfiltered through celite and
  2. concentrationconcentrated in vacuo
  3. extractionThe organic layer was extracted with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customPurification by silica gel chromatography (0-20% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-f0a6183c04844b6ba3fc7b2dc34947f0
Source dataset
uspto-grants-2015_12
Patent number
US09206131B2

Reaction notes

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