Iodine → 2-Chloro-4-iodo-5-(methoxymethoxy)pyridine

HRID 422099Notes

Reaction equation

HRID 422099 reaction equation
C([Li])(C)(C)C.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][O:15][CH3:16])=[CH:9][N:8]=1.[I:17]I>C1COCC1.C(OCC)(=O)C.O>[Cl:6][C:7]1[CH:12]=[C:11]([I:17])[C:10]([O:13][CH2:14][O:15][CH3:16])=[CH:9][N:8]=1

Participants

7

Reactant 3

HCID 807IodineHCID 587641932-chloro-5-(MethoxyMethoxy)pyridineHCID 178418306HCID 178418306, compound

Product 1

HCID 587641152-Chloro-4-iodo-5-(methoxymethoxy)pyridineYield 58.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-70 °C

Procedure

Add tert-buty lithium (1.7 M in pentane, 72 mL, 123 mmol) to a solution of 2-chloro-5-methoxymethoxy-pyridine (10.8 g, 62 mmol) in THF (300 mL) at −70° C. dropwise over 10 min. Stir the resulting solution at −70° C. for 30 min. Add a solution of iodine (23 g, 92 mmol) in THF (150 mL) dropwise over 30 min. Stir the resulting solution at −70° C. for 1 hour. Remove the ice bath and allow the reaction to warm to room temperature. Dilute the mixture with ethyl acetate and water and isolate the phases. Extract the aqueous phase with two portions of ethyl acetate. Combine the organic extracts and wash with two portions of aqueous sodium thiosulfate, one portion of water, one portion of saturated aqueous sodium chloride, dry over sodium sulfate, filter and concentrate in vacuo. Triturate the resulting solid with hexane. Collect the solid by vacuum filtration and wash the solid with hexane. Dry the solid under vacuum to give the title compound (10.8 g, 58%) as a brown solid. 1H NMR (400 MHz, DMSO-d6) δ 8.08 (s, 1H), 7.98 (s, 1H), 5.43 (s, 2H), 3.40 (s, 3H).

Workup

  1. stirringStir the resulting solution at −70° C. for 1 hour
  2. customRemove the ice bath
  3. customthe reaction
  4. temperatureto warm to room temperature
  5. customisolate the phases
  6. extractionExtract the aqueous phase with two portions of ethyl acetate
  7. washwash with two portions of aqueous sodium thiosulfate, one portion of water, one portion of saturated aqueous sodium chloride
  8. dry with materialdry over sodium sulfate
  9. filtrationfilter
  10. concentrationconcentrate in vacuo
  11. customTriturate the resulting solid with hexane
  12. customCollect the solid
  13. filtrationby vacuum filtration
  14. washwash the solid with hexane
  15. customDry the solid under vacuum

Sources & evidence

ORD record
ord-684c0ba570a44e70b1555fb3f5ccef98
Source dataset
uspto-grants-2012_01
Patent number
US08101628B2

Reaction notes

Loading…