2-Fluoro-4-iodoaniline → Ethyl 6-chloro-4-(2-fluoro-4-iodoanilino)nicotinate

HRID 917691Notes

Reaction equation

HRID 917691 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.[F:14][C:15]1[CH:21]=[C:20]([I:22])[CH:19]=[CH:18][C:16]=1[NH2:17]>CCO.Cl>[Cl:13][C:4]1[CH:3]=[C:2]([NH:17][C:16]2[CH:18]=[CH:19][C:20]([I:22])=[CH:21][C:15]=2[F:14])[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=1

Participants

5

Reactant 2

HCID 1856942-Fluoro-4-iodoanilineHCID 600045Ethyl 4,6-dichloropyridine-3-carboxylate

Product 1

HCID 23631002Ethyl 6-chloro-4-(2-fluoro-4-iodoanilino)nicotinate

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

Ethyl 4,6-dichloronicotinate (18.60 g, 84.40 mmol) and 2-fluoro-4-iodoaniline (20.0 g, 84.40 mmol) were dissolved in EtOH (80 mL), to which was added conc. HCl (6 drops). This mixture was heated, in an oil bath at 90° C., for 24 h. The solvent was evaporated under reduced pressure. The residue was partitioned between water (100 mL) and EtOAc (400 mL). The organic layer was washed sequentially with saturated NaHCO3 and saturated NaCl, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified on SiO2 using flash chromatography (eluent:5-10% EtOAc/Hexanes) to afford ethyl 6-chloro-4-(2-fluoro-4-iodoanilino)nicotinate as an off white solid (22.0 g, 62%). 1H NMR [(CD3)2SO, 400 MHz] δ 9.62 (s, 1H), 8.69 (s, 1H), 7.82 (dd, J=9.9, 1.9 Hz, 1H), 7.61-7.66 (m, 1H), 7.33 (t, J=8.5 Hz, 1H), 6.67 (d, J=1.8 Hz, 1H), 4.37 (q, J=7.1 Hz, 2H), 1.35 (t, J=7.1 Hz, 3H). Anal. Calcd for C14H11ClFIN2O2: C, 39.98; H, 2.64; N, 6.66. Found: C, 40.4; H, 2.38; N, 6.59.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customThe residue was partitioned between water (100 mL) and EtOAc (400 mL)
  3. washThe organic layer was washed sequentially with saturated NaHCO3 and saturated NaCl
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified on SiO2 using flash chromatography (eluent:5-10% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-bf1f4bc7c3724738a1bc9c7e697c5e32
Source dataset
uspto-grants-2007_09
Patent number
US07273877B2

Reaction notes

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