Potassium Carbonate → methyl [2-fluoro-4-(2-oxo-1(2H)-pyridinyl)phenyl]acetate

HRID 1261592Notes

Reaction equation

HRID 1261592 reaction equation
[F:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[CH:4][C:3]=1[CH2:9][C:10]([O:12][CH3:13])=[O:11].C(=O)([O-])[O-].[K+].[K+].[OH:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1>CS(C)=O.[Cu]I>[F:1][C:2]1[CH:7]=[C:6]([N:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]2=[O:20])[CH:5]=[CH:4][C:3]=1[CH2:9][C:10]([O:12][CH3:13])=[O:11]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 187102252-Fluoro-4-iodo phenyl acetic acid methyl esterHCID 178516071HCID 178516071, compound

Product 1

HCID 86216773methyl [2-fluoro-4-(2-oxo-1(2H)-pyridinyl)phenyl]acetateYield 39%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
125 °C

Procedure

Part G. To methyl (2-fluoro-4-iodophenyl)acetate (1.0 g, 3.4 mmol) in dimethylsulfoxide (68 mL) was added potassium carbonate (1.9 g, 14 mmol) and 2-hydroxypyridine (650 mg, 6.8 mmol). The resulting mixture was degassed (alternate vacuum/nitrogen three times), and copper(I) iodide (650 mg, 3.4 mmol) was added in one portion. The light green mixture was again degassed (vac/N2) and warmed to 125° C. After 14 h, the brown-black mixture was cooled and poured into saturated aqueous ammonium hydroxide (50 mL) and ethyl acetate (100 mL). The layers were separated, and the organic layers were washed with water (2×50 mL) and saturated aqueous sodium chloride. The organic layers were concentrated, and the resulting residue was purified by radial chromatography (20-100% ethyl acetate in hexanes) to afford methyl [2-fluoro-4-(2-oxo-1(2H)-pyridinyl)-phenyl]acetate (340 mg, 39%) as a green-brown solid. LC/MS (ESP+): 262.2 (M+H)+. 1H NMR (CDCl3) δ 7.22-7.36 (m, 3H), 7.08 (t, 2H), 6.54 (d, 1H), 6.18 (t, 1H), 3.63 (s, 5H).

Workup

  1. additionwas added in one portion
  2. customThe light green mixture was again degassed (vac/N2)
  3. temperaturethe brown-black mixture was cooled
  4. additionpoured into saturated aqueous ammonium hydroxide (50 mL) and ethyl acetate (100 mL)
  5. customThe layers were separated
  6. washthe organic layers were washed with water (2×50 mL) and saturated aqueous sodium chloride
  7. concentrationThe organic layers were concentrated
  8. customthe resulting residue was purified by radial chromatography (20-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-ca73e6a5d71743f6a3f854ea1d3c6a30
Source dataset
uspto-grants-2013_06
Patent number
US08470854B2

Reaction notes

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