1-Chloro-4-(chloromethyl)benzene → 3-[(4-Chlorophenyl)methoxy]pyridine

HRID 1995842Notes

Reaction equation

HRID 1995842 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1.[Cl:10][C:11]1[CH:18]=[CH:17][C:14]([CH2:15]Cl)=[CH:13][CH:12]=1>CN(C)C=O>[Cl:10][C:11]1[CH:18]=[CH:17][C:14]([CH2:15][O:3][C:4]2[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=2)=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 79713-HydroxypyridineHCID 24758Sodium hydride

Product 1

HCID 198310963-[(4-Chlorophenyl)methoxy]pyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To prewashed NaH (3X 20 ml hexane) (2.52 g active NaH, 105 mmol) in dimethylformamide (DMF) (50 ml) is added 3-hydroxypyridine (10.0 g, 105 mmol) in DMF (50 ml) with cooling over 0.5 hour. The reaction mixture is stirred at RT for 1 hour and is then cooled to 15°. To this is rapidly added 4-chlorobenzyl chloride (16.25 g, 99.8 mmol) in 5 ml of DMF. The reaction is allowed to warm to RT, and is then poured into ice and extracted with chloroform (3X). The chloroform layers are combined, washed with water and with brine, dried over calcium sulfate and rotoevaporated. The crude product is poured into ice and extracted with ether (3X). The combined ether layers are washed with water and with brine, and dried over calcium sulfate to give 3-(4-chlorobenzyloxy)pyridine.

Workup

  1. temperaturewith cooling over 0.5 hour
  2. temperatureis then cooled to 15°
  3. temperatureto warm to RT
  4. additionis then poured into ice
  5. extractionextracted with chloroform (3X)
  6. washwashed with water and with brine
  7. dry with materialdried over calcium sulfate
  8. additionThe crude product is poured into ice
  9. extractionextracted with ether (3X)
  10. washThe combined ether layers are washed with water and with brine
  11. dry with materialdried over calcium sulfate

Sources & evidence

ORD record
ord-c45abf01ce244e10873390218586cd11
Source dataset
uspto-grants-1983_09
Patent number
US04406689

Reaction notes

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