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

HRID 1064048Notes

Reaction equation

HRID 1064048 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

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 (ESI+): 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-3474e3568aec4e35b95858d0a72b9132
Source dataset
uspto-grants-2005_11
Patent number
US06967208B2

Reaction notes

Loading…