Lithium Hydroxide → 4-(2-oxopyridin-1(2H)-yl)benzoyl chloride

HRID 892303Notes

Reaction equation

HRID 892303 reaction equation
IC[C:3]1[CH:11]=[CH:10][C:6]([C:7]([O-:9])=O)=[CH:5][CH:4]=1.[OH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[Li+].[OH-].S(Cl)([Cl:29])=O>C1COCC1.ClCCl.[Cu]I.CN(C=O)C.O>[O:12]=[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]1[C:3]1[CH:4]=[CH:5][C:6]([C:7]([Cl:29])=[O:9])=[CH:10][CH:11]=1

Participants

11

Reactant 5

HCID 3939Lithium HydroxideHCID 10796Cesium carbonateHCID 24386Thionyl ChlorideHCID 222405234-IodomethylbenzoateHCID 178516071HCID 178516071, compound

Product 1

HCID 222404154-(2-oxopyridin-1(2H)-yl)benzoyl chloride

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

Part A. To a solution of 4-iodomethylbenzoate is added 2-hydroxypyridine (1 eq), cesium carbonate (1.5 eq) followed by catalytic CuI. The reaction mixture is heated at 100° C. overnight, cooled, and quenched with water. The organics are extracted with ethyl acetate, dried, and evaporated to afford crude product which is purified via silica gel column chromatography (hexane:ethylacetate) to afford the coupled product. Part B. To the product from part A in THF is added LiOH (excess of 1 eq) and water. The reaction mixture is stirred at rt overnight and quenched with dilute HCl. The desired carboxylic acid intermediate is extracted with ethyl acetate, dried, and evaporated to afford the product. Part C. To the product from part B in dichloromethane is added 1 equivalent of thionyl chloride along with cat. DMF. The reaction mixture is stirred at rt overnight and concentrated to afford 4-(2-oxo-pyridin-1-yl)-benzoyl chloride. Part D. To a solution of 2-nitro-5-chloro-benzoylchloride in dichloromethane is added 2-amino-5-chloropyridine (1 eq) and DMAP (excess of 2 eq). The reaction mixture is stirred at rt overnight, quenched with water, and the organics extracted with ethylacetate and dried (magnesium sulfate). Evaporation affords the coupled product. Part E. The product from part A was dissolved in ethyl acetate. To this solution is added 3 equivalents of tin chloride, and the reaction mixture stirred at rt for 4 h. The reaction mixture is quenched with sat'd ammonium hydroxide solution and the organics extracted with ethyl acetate, dried, and evaporated to afford the anilino product. Part F. The product from part B was dissolved in dichloromethane and to this solution is added 4-(2-oxopyridin-1-yl)-benzoyl chloride (1 eq) and DMAP (excess of 2 eq). The reaction mixture is stirred at rt overnight, concentrated, and purified via reverse phase prep. HPLC (acetonitrile/water/TFA) to afford the title compound.

Workup

  1. temperaturecooled
  2. customquenched with water
  3. extractionThe organics are extracted with ethyl acetate
  4. customdried
  5. customevaporated
  6. customto afford crude product which
  7. customis purified via silica gel column chromatography (hexane:ethylacetate)
  8. customto afford the coupled product
  9. customquenched with dilute HCl
  10. extractionThe desired carboxylic acid intermediate is extracted with ethyl acetate
  11. customdried
  12. customevaporated
  13. customto afford the product
  14. stirringThe reaction mixture is stirred at rt overnight
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-349e497f1f1f4aa0954a7d8d6f5d7ab3
Source dataset
uspto-grants-2006_02
Patent number
US07005435B2

Reaction notes

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