Dichloroacetic Acid → 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-1-(2,6-difluorophenyl)-5-iodo-6-methylpyridin-2(1H)-one

HRID 1831986Notes

Reaction equation

HRID 1831986 reaction equation
[Br:1][C:2]1[C:3](=[O:27])[N:4]([C:19]2[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=2[F:26])[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].[I:28]N1C(=O)CCC1=O.ClC(Cl)C(O)=O>ClC(Cl)C>[Br:1][C:2]1[C:3](=[O:27])[N:4]([C:19]2[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=2[F:26])[C:5]([CH3:18])=[C:6]([I:28])[C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

5

Reactant 3

HCID 6597Dichloroacetic AcidHCID 120273N-IodosuccinimideHCID 220501433-Bromo-4-[(2,4-difluorobenzyl)oxy]-1-(2,6-difluorophenyl)-6-methylpyridin-2(1H)-one

Product 1

HCID 220499923-Bromo-4-[(2,4-difluorobenzyl)oxy]-1-(2,6-difluorophenyl)-5-iodo-6-methylpyridin-2(1H)-oneYield 32.4%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A solution of 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-1-(2,6-difluorophenyl)-6-methylpyridin-2(1H)-one (0.3 g, 0.00068 mol) and N-iodosuccinimide (0.22 g, 0.00098 mol) in dichloroethane, containing dichloroacetic acid (0.1 mL) was heated to reflux for 6 h under argon atmosphere. After the removal of the solvents under reduced pressure, the residue was partitioned between, dichloromethane (20 mL) and 5% sod. sulphite (10 mL). The organic phase was washed with water, dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by flash chromatography (25% EtOAc in hexane) to afford the title compound (0.125 g, 32%) as a pale yellow powder: 1H NMR (CDCl3/400 MHz) δ 7.68 (m, 1H), 7.46 (m, 1H), 7.11 (m, 2H), 6.95 (m, 1H), 6.85 (m, 1H), 5.23 (s, 2H), and 2.38 (s, 3H); 19F NMR (CDCl3) δ−109.15 (m), −112.95 (m), −118.50 (m); ES-HRMS m/z 567.9014 (M+H C19H12NO2F4BrI requires 567.9027).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 6 h under argon atmosphere
  3. customAfter the removal of the solvents under reduced pressure
  4. customthe residue was partitioned between, dichloromethane (20 mL) and 5% sod
  5. washThe organic phase was washed with water
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash chromatography (25% EtOAc in hexane)

Sources & evidence

ORD record
ord-2a85c6d3d02249c1abea92b60618155d
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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