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

HRID 367108Notes

Reaction equation

HRID 367108 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 400 mL water and extracted with Et2O (5×300 mL). The combined Et2O extracts were washed with 50% brine (6×300 mL) and dried (MgSO4). The solvent was evaporated in vacuo and the crude product was recrystallized from Et2O to afford 161 g (72%) of the title product, mp 63-68° C. 1H NMR (CDCl3, 300 MHz) δ 8.37-8.27 (m, 2H), 7.5-7.35 (m, 6H), 5.1 (s, 1H). MS (DCI/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 400 mL water
  4. extractionextracted with Et2O (5×300 mL)
  5. washThe combined Et2O extracts were washed with 50% brine (6×300 mL)
  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-e45358b618784bcf9e712a0e8bf4b423
Source dataset
uspto-grants-2000_10
Patent number
US06133253

Reaction notes

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