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

HRID 2185719Notes

Reaction equation

HRID 2185719 reaction equation
[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Br:11][C:12]1[CH:13]=[N:14][CH:15]=[C:16](Br)[CH:17]=1>CN(C=O)C>[CH2:3]([O:10][C:16]1[CH:15]=[N:14][CH:13]=[C:12]([Br:11])[CH:17]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 693693,5-Dibromopyridine

Product 1

HCID 153891983-(Benzyloxy)-5-bromopyridineYield 72.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

NaH (60% in mineral oil) (40.9 g 1.0225 mol) in 800 mL of DMF was cooled to 0° C., and benzyl alcohol (105 mL 1.014 mol) was added slowly. The reaction mixture was stirred for 1 hour at 20° C., then 3,5-dibromopyridine (200.4 g, 846 mmol) was added and the mixture was stirred for 16 hours. The mixture was quenched with saturated NH4Cl (500 mL), diluted with water and extracted with Et2O. The combined Et2O extracts were washed with 50% brine and dried (MgSO4). The solvent was evaporated in vacuo and the crude product was recrystallized from Et2O to afford the title product (161 g,72%): mp 63-68° C.; 1H NMR (CDCl3, 300 MHz) δ8.37-8.27 (m, 2H), 7.5-7.35 (m, 6H), 5.1 (s, 1H); MS (CI/NH3) m/z 264, 266 (M+H)+.

Workup

  1. stirringthe mixture was stirred for 16 hours
  2. customThe mixture was quenched with saturated NH4Cl (500 mL)
  3. additiondiluted with water
  4. extractionextracted with Et2O
  5. washThe combined Et2O extracts were washed with 50% brine
  6. dry with materialdried (MgSO4)
  7. customThe solvent was evaporated in vacuo
  8. customthe crude product was recrystallized from Et2O

Sources & evidence

ORD record
ord-342d459899424564bbb9036a1b15d26c
Source dataset
uspto-grants-2002_06
Patent number
US06403575B1

Reaction notes

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