Benzyl Alcohol → 2-(Benzyloxy)-6-chloro-4-iodopyridine

HRID 1253557Notes

Reaction equation

HRID 1253557 reaction equation
[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Cl:11][C:12]1[CH:17]=[C:16]([I:18])[CH:15]=[C:14](Cl)[N:13]=1.[Cl-].[NH4+]>C1COCC1.C(OCC)(=O)C>[CH2:3]([O:10][C:14]1[CH:15]=[C:16]([I:18])[CH:17]=[C:12]([Cl:11])[N:13]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 117373932,6-Dichloro-4-iodopyridine

Product 1

HCID 866570572-(Benzyloxy)-6-chloro-4-iodopyridine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of sodium hydride (1.24 g, 31.0 mmol, 60 wt % in mineral oil) in THF (30.4 mL) at 0° C. was added benzyl alcohol (2.09 mL, 20.1 mmol) dropwise via syringe. After stirring at 0° C. for 30 mins, 2,6-dichloro-4-iodopyridine (5.00 g, 18.3 mmol) in THF (5 mL) was added dropwise via syringe. The reaction mixture was warmed to room temperature and stirred for 3 hours. The reaction was cooled down to 0° C., and saturated aqueous ammonium chloride was slowly added to quench the reaction. The reaction mixture was allowed to warm to room temperature, diluted with ethyl acetate, and washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium thiosulfate. The organic layer was separated and the aqueous layer was back extracted two times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (ethyl acetate/ioshexane gradient) to give 2-(benzyloxy)-6-chloro-4-iodopyridine. LRMS (ESI) calculated for C12H10ClINO [M+H]+, 345.9; found 345.8.

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. stirringstirred for 3 hours
  3. temperatureThe reaction was cooled down to 0° C.
  4. customto quench
  5. customthe reaction
  6. temperatureto warm to room temperature
  7. washwashed with saturated aqueous sodium bicarbonate and saturated aqueous sodium thiosulfate
  8. customThe organic layer was separated
  9. extractionthe aqueous layer was back extracted two times with ethyl acetate
  10. dry with materialThe combined organic layers were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by column chromatography on silica gel (ethyl acetate/ioshexane gradient)

Sources & evidence

ORD record
ord-873ea2192cad45538cecef110adef3eb
Source dataset
uspto-grants-2013_06
Patent number
US08455477B2

Reaction notes

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