Benzyl Alcohol → 3-(Benzyloxy)-5-bromopyridine

HRID 650555Notes

Reaction equation

HRID 650555 reaction equation
[Na].[CH2:2]([OH:9])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Br:10][C:11]1[CH:12]=[N:13][CH:14]=[C:15](Br)[CH:16]=1>O.[Cu]>[Br:10][C:11]1[CH:12]=[N:13][CH:14]=[C:15]([O:9][CH2:2][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)[CH:16]=1

Participants

6

Reactant 3

HCID 244Benzyl Alcohol2×HCID 693693,5-DibromopyridineHCID 5360545Sodium

Product 1

HCID 153891983-(Benzyloxy)-5-bromopyridineYield 56.9%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

Under a nitrogen atmosphere, small pieces of sodium (1.48 g, 64.4 mmol) were added to benzyl alcohol (17.11 g, 158.0 mmol), and the mixture was stirred and heated at 70° C. for 18 h. To the stirring, viscous mixture was added 3,5-dibromopyridine (5.00 g, 21.1 mmol), copper powder (255 mg, 4.0 mmol), and benzyl alcohol (15 mL). The mixture was further heated at 100° C. for 48 h. The reaction mixture was allowed to cool to ambient temperature, diluted with water (50 mL), and extracted with diethyl ether (5×50 mL). The combined ether extracts were dried (Na2SO4), filtered, and concentrated by rotary evaporation. Vacuum distillation removed excess benzyl alcohol, bp 68-72° C. at 2.6 mm Hg. Further vacuum distillation afforded 3.17 g (38.0%) of 3-bromo-5-benzyloxypyridine as a white, crystalline solid, mp 64-66° C.

Workup

  1. temperatureThe mixture was further heated at 100° C. for 48 h
  2. temperatureto cool to ambient temperature
  3. extractionextracted with diethyl ether (5×50 mL)
  4. dry with materialThe combined ether extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation
  7. distillationVacuum distillation
  8. customremoved excess benzyl alcohol, bp 68-72° C. at 2.6 mm Hg
  9. distillationFurther vacuum distillation

Sources & evidence

ORD record
ord-bb4f9429ef87463cbd425b1fd524fadc
Source dataset
uspto-grants-2001_08
Patent number
US06274606B1

Reaction notes

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