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

HRID 1995824Notes

Reaction equation

HRID 1995824 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 (3×20 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 (3×). 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 (3×). 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 (3×)
  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 (3×)
  10. washThe combined ether layers are washed with water and with brine
  11. dry with materialdried over calcium sulfate

Sources & evidence

ORD record
ord-0511eafda5af407da53bdf7c2baa551c
Source dataset
uspto-grants-1983_09
Patent number
US04406690

Reaction notes

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