Lithium Chloride → HCID 66721004, compound

HRID 1040349Notes

Reaction equation

HRID 1040349 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:16]2[N:21]=[C:20]([C:22]([O:24][CH3:25])=[O:23])[CH:19]=[CH:18][C:17]=2OS(C(F)(F)F)(=O)=O)[CH:12]=[CH:13][C:14]=1[Cl:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=1)CCC.[Cl-].[Li+].[F-].[K+]>CN(C=O)C.CCOC(C)=O.[Cu]I.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].Cl[Pd]Cl>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:16]2[C:17]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=3)=[CH:18][CH:19]=[C:20]([C:22]([O:24][CH3:25])=[O:23])[N:21]=2)[CH:12]=[CH:13][C:14]=1[Cl:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

10

Reactant 4

HCID 433294Lithium ChlorideHCID 522689Potassium FluorideHCID 6077842-(Tributylstannyl)pyridineHCID 86637361HCID 86637361, compound

Product 1

HCID 66721004HCID 66721004, compoundYield 55.7%

Reagents, catalysts & solvents 5

HCID 24290Palladium ChlorideCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Stir a suspension of 0.5 g (1 mmol) of methyl 6-[3-(benzyloxy)-4-chlorophenyl]-5-{[(trifluoromethyl)sulphonyl]oxy}pyridine-2-carboxylate, 0.44 g (1.2 mmol) of 2-tri-n-butylstannylpyridine and 42 mg (1 mmol) of anhydrous lithium chloride in 2 mL of anhydrous DMF for 10 min while bubbling with argon, then add 9.5 mg (0.05 mmol) of CuI, 45 mg (0.05 mmol) of Pd2(dba)3 and 27 mg (0.05 mmol) of PdCl2 (dppf) and then heat the reaction mixture to 90° C. After stirring for 5 h at 90° C., cool the mixture to RT, take up in 30 ml of EtOAc, treat and stir for 15 minutes with 30 mL of a 5 wt. % aqueous solution of potassium fluoride. Then filter the two-phase mixture on a bed of celite, and rinse the celite with 30 mL of EtOAc. Wash the organic phase with 4×60 mL of water, dry over Na2SO4 and concentrate at reduced pressure. Purify the residue obtained by chromatography on a silica column, eluting with a toluene/EtOAc gradient from 0 to 15% of EtOAc. After concentration under reduced pressure, we obtain 240 mg of methyl 2′-[3-(benzyloxy)-4-chlorophenyl]-2,3′-bipyridine-6′-carboxylate in the form of oil.

Workup

  1. customwhile bubbling with argon
  2. stirringAfter stirring for 5 h at 90° C.
  3. temperaturecool the mixture to RT
  4. additiontreat
  5. filtrationThen filter the two-phase mixture on a bed of celite
  6. washrinse the celite with 30 mL of EtOAc
  7. washWash the organic phase with 4×60 mL of water
  8. dry with materialdry over Na2SO4
  9. concentrationconcentrate at reduced pressure
  10. customPurify the residue
  11. customobtained by chromatography on a silica column
  12. washeluting with a toluene/EtOAc gradient from 0 to 15% of EtOAc
  13. concentrationAfter concentration under reduced pressure, we

Sources & evidence

ORD record
ord-31bee4da1e4d45ca803c7ae264ee349c
Source dataset
uspto-grants-2013_10
Patent number
US08552201B2

Reaction notes

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