Potassium Carbonate → 4-(5-chloro-4-hydroxy-2-oxopyridin-1(2H)-yl)-2-fluorobenzonitrile

HRID 386587

Reaction equation

HRID 386587 reaction equation
[F:1][C:2]1[CH:9]=[C:8](I)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[Cl:11][C:12]1[C:13]([OH:19])=[CH:14][C:15](=[O:18])[NH:16][CH:17]=1.COC1C2C(=C3C(=CC=2)C(OC)=CC=N3)N=CC=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.O.Cl.[Cu]I>[Cl:11][C:12]1[C:13]([OH:19])=[CH:14][C:15](=[O:18])[N:16]([C:8]2[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([F:1])[CH:9]=2)[CH:17]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 27745182-Fluoro-4-iodobenzonitrileHCID 104622984,7-Dimethoxy-1,10-phenanthrolineHCID 54679224Gimeracil

Product 1

HCID 673665324-(5-chloro-4-hydroxy-2-oxopyridin-1(2H)-yl)-2-fluorobenzonitrileYield 74.7%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 313Hydrochloric AcidSolventHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 2-fluoro-4-iodobenzonitrile (4000 mg, 16.19 mmol), 5-chloro-4-hydroxypyridin-2(1H)-one (2357 mg, 16.19 mmol), 4,7-dimethoxy-1,10-phenanthroline (778 mg, 3.24 mmol), copper(I) iodide (617 mg, 3.24 mmol) and potassium carbonate (4476 mg, 32.4 mmol) in DMSO (40 mL) was stirred at 140° C. under N2 for 3 hrs. After cooling to room temperature, the reaction mixture was diluted with H2O (50 mL) and 1N HCl was added to adjust the pH to ˜2 (pH paper). The resulting mixture was extracted with EtOAc (400 mL, 2×). The combined extracts were dried (Na2SO4) and evaporated under reduced pressure to give black oil. The residue was purified by flash chromatography on silica gel (0-7% MeOH/CH2Cl2) to give brown oil (3.2 g, 43.3%). MS (ESI) 265 (M+H).

Workup

  1. temperatureAfter cooling to room temperature
  2. additionwas added
  3. extractionThe resulting mixture was extracted with EtOAc (400 mL, 2×)
  4. dry with materialThe combined extracts were dried (Na2SO4)
  5. customevaporated under reduced pressure
  6. customto give black oil
  7. customThe residue was purified by flash chromatography on silica gel (0-7% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-5d6afe5221a64677b319636073ff25ea
Source dataset
uspto-grants-2013_02
Patent number
US08372837B2

Linked notes

Loading…