3-Chlorophenol → [2-(3-Chloro-phenoxy)-5-fluoro-pyridin-3-yl]-(3,4-dihydro-2H-quinolin-1-yl)-methanone

HRID 1877351Notes

Reaction equation

HRID 1877351 reaction equation
Cl[C:2]1[C:7]([C:8]([N:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][CH2:12][CH2:11]2)=[O:9])=[CH:6][C:5]([F:20])=[CH:4][N:3]=1.[Cl:21][C:22]1[CH:23]=[C:24]([OH:28])[CH:25]=[CH:26][CH:27]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.[Cu]I.[Cu]>[Cl:21][C:22]1[CH:23]=[C:24]([CH:25]=[CH:26][CH:27]=1)[O:28][C:2]1[C:7]([C:8]([N:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][CH2:12][CH2:11]2)=[O:9])=[CH:6][C:5]([F:20])=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 79333-ChlorophenolHCID 11430Potassium CarbonateHCID 86641254(2-Chloro-5-fluoro-pyridin-3-yl)-(3,4-dihydro-2H-quinolin-1-yl)-methanone

Product 1

HCID 46195846[2-(3-Chloro-phenoxy)-5-fluoro-pyridin-3-yl]-(3,4-dihydro-2H-quinolin-1-yl)-methanoneYield 6.2%

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
200 °C

Procedure

To a solution of (2-chloro-5-fluoro-pyridin-3-yl)-(3,4-dihydro-2H-quinolin-1-yl)-methanone (53.2 mg, 0.18 mmol, 1.0 equiv) and 3-chloro-phenol (23.5 mg, 0.18 mmol, 1.0 equiv; [CAS RN 108-43-0]) in acetonitrile (1 mL) was added potassium carbonate (50.7 mg, 0.37 mmol, 2.0 equiv; [CAS RN 584-08-7]), copper(I) iodide (3.5 mg, 0.018 mmol, 0.1 equiv; [CAS RN 7681-65-4]) and copper(0) nanopowder with an averaged particle size of 100 nm (3.5 mg, 0.055 mmol, 0.3 equiv; [CAS RN 7440-50-8]). The reaction mixture was heated by microwave irradiation to 200° C. for 90 min. Removal of the solvent under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 4.3 mg (6%) of the title compound. MS (ISP): 383.2 [M+H]+.

Workup

  1. customRemoval of the solvent
  2. customunder reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column
  3. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
  4. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

Sources & evidence

ORD record
ord-9e4b00f613624787a23ff197fa2bd132
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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