Isopropanol → 3-Chloro-2-isopropoxypyridine

HRID 1620347Notes

Reaction equation

HRID 1620347 reaction equation
[H-].[Na+].[CH:3]([OH:6])([CH3:5])[CH3:4].Cl[C:8]1[C:13]([Cl:14])=[CH:12][CH:11]=[CH:10][N:9]=1>C1COCC1>[Cl:14][C:13]1[C:8]([O:6][CH:3]([CH3:5])[CH3:4])=[N:9][CH:10]=[CH:11][CH:12]=1

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 169882,3-DichloropyridineHCID 24758Sodium hydride

Product 1

HCID 107735093-Chloro-2-isopropoxypyridineYield 89.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

To a 3-necked flask equipped with a dropping funnel, thermometer and a condenser was added sodium hydride (64.10 g; 1.07 mol) followed by THF (1.65 L). The suspension was cooled to 5° C. and iso-propanol (128 mL; 1.07 mol) was added dropwise over 50 minutes. Upon complete addition the ice bath was removed and the mixture was brought to room temperature and was left to stir for 1 hour. Then 2,3-dichloropyridine (154.6 g; 1.11 mol) was added and the reaction mixture brought to a gentle reflux and left to stir for 18 hours. The reaction mixture was cooled to 5-10° C. and was carefully quenched with brine:water mixture (50:50; 100 mL) followed by water (300 mL). The aqueous layer was extracted with EtOAc (3×600 mL), the organic layers combined and washed with brine, dried (MgSO4), filtered and evaporated to give the title compound as a dark red oil (164.1 g; 89%).

Workup

  1. customTo a 3-necked flask equipped with a dropping funnel
  2. customwas removed
  3. customwas brought to room temperature
  4. waitwas left
  5. temperaturea gentle reflux
  6. waitleft
  7. stirringto stir for 18 hours
  8. temperatureThe reaction mixture was cooled to 5-10° C.
  9. customwas carefully quenched with brine
  10. extractionThe aqueous layer was extracted with EtOAc (3×600 mL)
  11. washwashed with brine
  12. dry with materialdried (MgSO4)
  13. filtrationfiltered
  14. customevaporated

Sources & evidence

ORD record
ord-15c577c438d14071b886578caac4ab45
Source dataset
uspto-grants-2014_07
Patent number
US08772343B2

Reaction notes

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