Hydrochloric Acid → Ethyl 6-chloro-4-(phenylamino)nicotinate

HRID 1930297Notes

Reaction equation

HRID 1930297 reaction equation
Cl[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=[C:4]([Cl:13])[CH:3]=1.[NH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.Cl>CCO>[Cl:13][C:4]1[CH:3]=[C:2]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6115AnilineHCID 600045Ethyl 4,6-dichloropyridine-3-carboxylate

Product 1

HCID 59212513Ethyl 6-chloro-4-(phenylamino)nicotinateYield 50%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of ethyl 4,6-dichloronicotinate (16 g, 73 mmol), aniline (8.2 g, 88 mmol) and cone. HCl (0.5 mL) in EtOH (100 mL) was heated at reflux overnight. The solvent was removed under reduced pressure. Water was added and the solution was basified to pH 8 and extracted with EtOAc. The combined extracts were washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by chromatography to give ethyl 6-chloro-4-(phenylamino)nicotinate (10 g, 50% yield). 1H NMR (40 MHz, DMSO-d6): δ 9.73 (s, 1 H), 8.67 (s, 1 H), 7.50-7.46 (m, 2 H), 7.36-7.31 (m, 3 H), 6.78 (s, 1 H), 4.37 (q, J=7.2 Hz, 2 H), 1.35 (t, J=7.2 Hz, 3 H).

Workup

  1. temperatureat reflux overnight
  2. customThe solvent was removed under reduced pressure
  3. additionWater was added
  4. extractionextracted with EtOAc
  5. washThe combined extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by chromatography

Sources & evidence

ORD record
ord-8c53aa39f8514f3faab935c39d0d8fef
Source dataset
uspto-grants-2012_05
Patent number
US08188113B2

Reaction notes

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