Cesium fluoride → Methyl 5''-chloro-[2,2':5',3''-terpyridine]-3'-carboxylate

HRID 1802358Notes

Reaction equation

HRID 1802358 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[N:10][C:11](Cl)=[C:12]([C:14]([O:16][CH3:17])=[O:15])[CH:13]=2)[CH:5]=[N:6][CH:7]=1.C([Sn](CCCC)(CCCC)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=1)CCC.[F-].[Cs+]>CN(C)C=O.C(OCC)(=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([C:14]([O:16][CH3:17])=[O:15])[C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=3)=[N:10][CH:9]=2)[CH:5]=[N:6][CH:7]=1

Participants

8

Reactant 3

HCID 25953Cesium fluorideHCID 6077842-(Tributylstannyl)pyridineHCID 59187390Methyl 5',6-dichloro-[3,3'-bipyridine]-5-carboxylate

Product 1

HCID 59187377Methyl 5''-chloro-[2,2':5',3''-terpyridine]-3'-carboxylate

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of methyl 5′,6-dichloro-3,3′-bipyridine-5-carboxylate (12-2, 7.6 g, 26.8 mmol, 1.0 equiv) in dimethylformamide (107 mL) was added 2-tri-n-butylstannylpyridine (13.8 g, 37.6 mmol, 1.4 equiv), cesium fluoride (12.2 g, 81.0 mmol, 3.0 equiv), copper (I) iodide (1.0 g, 5.4 mmol, 0.2 equiv), and tetrakis(triphenylphosphine)palladium(0) (3.1 g, 2.7 mmol, 0.1 equiv) and the system was heated to 80° C. for 2 h. The reaction mixture was cooled and diluted with ethyl acetate (300 mL) and the reaction mixture was filtered through a pad of celite. The reaction mixture was washed with water (3×100 mL) and brine (1×100 mL), dried over magnesium sulfate and concentrated. The residue was purified via normal phase chromatography (10 to 100% EtOAc in hexanes, silica) followed by chiral normal phase chromatography (Chiracel OD, 10 cm column, hexanes:IPA [1:1], flow rate 150 mL/min) to afford the desired product (12-3) as a white solid after concentration. ESI+MS [M+H]+ C17H12ClN3O2 calc'd 326.1. found 326.0.

Workup

  1. temperatureThe reaction mixture was cooled
  2. filtrationthe reaction mixture was filtered through a pad of celite
  3. washThe reaction mixture was washed with water (3×100 mL) and brine (1×100 mL)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified via normal phase chromatography (10 to 100% EtOAc in hexanes, silica)

Sources & evidence

ORD record
ord-6148513c4afe424996eec2a0ef809e6f
Source dataset
uspto-grants-2013_01
Patent number
US08349872B2

Reaction notes

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