Dichloroacetic Acid → (3-fluorobenzyl)-3-iodo-1H-pyridin-2-one

HRID 1831945Notes

Reaction equation

HRID 1831945 reaction equation
FC1C=C(F)C=CC=1CO[C:6]1[CH:11]=[CH:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=2)[C:8](=[O:20])[CH:7]=1.[I:26]N1C(=O)CCC1=O.ClC(Cl)C(O)=O>CC#N>[F:19][C:15]1[CH:14]=[C:13]([CH:18]=[CH:17][CH:16]=1)[CH2:12][N:9]1[CH:10]=[CH:11][CH:6]=[C:7]([I:26])[C:8]1=[O:20]

Participants

5

Reactant 3

HCID 6597Dichloroacetic AcidHCID 120273N-IodosuccinimideHCID 22050302HCID 22050302, compound

Product 1

HCID 79784710(3-fluorobenzyl)-3-iodo-1H-pyridin-2-oneYield 106%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 4-(2,4-difluorobenzyloxy)-1-(3-fluorobenzyl)-1H-pyridin-2-one (0.15 g, 0.43 mmol) and N-iodosuccinimide (0.10 g, 0.46 mmol) in CH3CN (3 mL) was added dichloroacetic acid (13 mg, 0.10 mmol), and the reaction mixture was heated to 60° C. for 4 h. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, and the residue was dissolved in methylene chloride. The organic solution was washed with a saturated solution of NaHCO3 and then brine, dried (Na2SO4), filtered and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent 90:10 methylene chloride/hexanes to 99:1 methylene chloride/methanol) provided 4-(2,4-difluorobenzyloxy)-[(3-fluorobenzyl)-3-iodo-1H-pyridin-2-one as a white solid (0.15 g, 77%): mp 164-167° C.; 1H NMR (300 MHz, CDCl3) δ 7.65-7.55 (m, 1H), 7.35-7.26 (m, 2H), 7.15-6.80 (m, 5H), 6.05 (d, J=6 Hz, 1H), 5.22 (s, 2H), 5.16 (s, 2H) ES HRMS m/z 472.0033 (M+H C19H14F31NO2 requires 472.0018).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. dissolutionthe residue was dissolved in methylene chloride
  4. washThe organic solution was washed with a saturated solution of NaHCO3
  5. dry with materialbrine, dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash column chromatography (silica, eluent 90:10 methylene chloride/hexanes to 99:1 methylene chloride/methanol)

Sources & evidence

ORD record
ord-5cabf8533a07426a86417a10cc136610
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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