Acetic Acid → HCID 58962857, compound

HRID 917740Notes

Reaction equation

HRID 917740 reaction equation
Cl[C:2]1[CH:12]=[C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[F:21])[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][N:3]=1.[CH3:22]OS(OC)(=O)=O.C(N(CC)CC)C.CC(O)=O.[OH2:40]>C(Cl)(Cl)Cl.CCO>[F:21][C:15]1[CH:16]=[C:17]([F:20])[CH:18]=[CH:19][C:14]=1[NH:13][C:11]1[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][N:3]([CH3:22])[C:2](=[O:40])[CH:12]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 962WaterHCID 6497Dimethyl SulfateHCID 8471TriethylamineHCID 58962861HCID 58962861, compound

Product 1

HCID 58962857HCID 58962857, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6212ChloroformSolvent

Conditions

Temperature
0 °C

Procedure

Ethyl 6-chloro-4-(2,4-difluoroanilino)nicotinate (1.00 g, 3.2 mmol) was dissolved in CHCl3 (35 ml) and cooled to 0° C. Me2SO4 (2.45 g, 19.5 mmol) was added dropwise over 5 min. The solution was allowed to warm to room temperature and then refluxed for 18 h. After cooling to room temperature, a mixture of triethylamine (9.9 ml), AcOH (6.6 ml) and EtOH (6.6 ml) was added. The reaction mixture was heated to reflux for a further 2 h then cooled and H2O (50 ml) was added. After partitioning between water and EtOAc, the organic layer was further washed with water, brine, dried (Na2SO4) and concentrated under reduced pressure to give crude ethyl 4-(2,4-difluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylate. Further purification by recrystallisation (EtOAc/Hexane) gave the desired product as a cream solid (0.55 g, 56%); m.p. (EtOAc/Hexane) 128-132° C. 1H NMR [400 MHz, CDCl3] δ 9.15 (br s, 1H), 8.21 (s, 1H), 7.36-7.30 (m, 1H), 6.95-6.87 (m, 2H), 5.66 (s, 1H), 4.35 (q, J=7.1 Hz, 2H), 3.54 (s, 3H), 1.40 (t, J=7.1 Hz, 3H).

Workup

  1. temperatureto warm to room temperature
  2. temperaturerefluxed for 18 h
  3. temperatureAfter cooling to room temperature
  4. additionwas added
  5. temperatureThe reaction mixture was heated
  6. temperatureto reflux for a further 2 h
  7. temperaturethen cooled
  8. customAfter partitioning between water and EtOAc
  9. washthe organic layer was further washed with water, brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated under reduced pressure
  12. customto give crude ethyl 4-(2,4-difluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylate
  13. customFurther purification
  14. customby recrystallisation (EtOAc/Hexane)

Sources & evidence

ORD record
ord-7e4a6b9cb6af40f3bbe655ce3a367a0d
Source dataset
uspto-grants-2007_09
Patent number
US07273877B2

Reaction notes

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