Benzyl Alcohol → 4-(Benzyloxy)pyridine

HRID 1917597Notes

Reaction equation

HRID 1917597 reaction equation
[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl.Cl[C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1.O>CN(C=O)C>[CH2:3]([O:10][C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 962WaterHCID 24758Sodium hydrideHCID 818524-Chloropyridine hydrochloride

Product 1

HCID 123288284-(Benzyloxy)pyridineYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
5 °C

Procedure

A flask is charged with NaH (60% dispersion in mineral oil, 0.72 g, 18.0 mmol) then suspended in DMF (30 mL) and cooled to 5° C. To this mixture is added benzyl alcohol (1.04 mL, 10.0 mmol) drop-wise. The mixture is stirred for 15 minutes then 4-chloropyridine-HCl (1.00 g, 6.67 mmol) is added in three portions over 5 min. The resulting mixture is stirred at 5° C. for 10 min then warmed to 60° C. and stirred for 1.5 h. The mixture is then cooled to 23° C., treated with water, and extracted with EtOAc. The combined organics are dried with MgSO4, filtered, and concentrated in vacuo. Purification of the crude by flash chromatography (SiO2, 5% EtOAc in hexanes to 50% EtOAc in hexanes) gives the title intermediate (1.10 g, 89%).

Workup

  1. stirringThe resulting mixture is stirred at 5° C. for 10 min
  2. temperaturethen warmed to 60° C.
  3. stirringstirred for 1.5 h
  4. temperatureThe mixture is then cooled to 23° C.
  5. extractionextracted with EtOAc
  6. dry with materialThe combined organics are dried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification of the crude by flash chromatography (SiO2, 5% EtOAc in hexanes to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-de86f075d9bf45bfbe99fd4b47eda8a0
Source dataset
uspto-grants-2013_12
Patent number
US08618300B2

Reaction notes

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