Benzyl Bromide → 4-(Benzyloxy)-2-bromopyridine

HRID 523918Notes

Reaction equation

HRID 523918 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][N:5]=1.[CH2:11](Br)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CCOC(C)=O>CN(C=O)C>[CH2:11]([O:10][C:8]1[CH:7]=[CH:6][N:5]=[C:4]([Br:3])[CH:9]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 7498Benzyl BromideHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 178516474HCID 178516474, compound

Product 1

HCID 153891994-(Benzyloxy)-2-bromopyridineYield 51.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NaH (761 mg, 19.83 mmol) was added portion wise to 2-bromo-4-hydroxypyridine (3 g, 17.24 mmol) in DMF (50 mL) at 0° C. under Ar(g). Then the reaction mixture was stirred at rt for 10 min after which it was again cooled down at 0° C. and benzyl bromide (2.15 mL, 18.10 mmol) was added. The reaction was stirred at it for 4 h, after which it was poured onto brine (200 mL) and EtOAc (200 mL) was added. The phases were separated and the organic phase was dried over MgSO4, filtered and subsequently evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography eluting with hexane/EtOAc (90:10 to 80:20) to furnish I as a white solid (2.331 g, 51%).

Workup

  1. temperaturewas again cooled down at 0° C.
  2. stirringThe reaction was stirred at it for 4 h
  3. additionwas added
  4. customThe phases were separated
  5. dry with materialthe organic phase was dried over MgSO4
  6. filtrationfiltered
  7. customsubsequently evaporated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography
  9. washeluting with hexane/EtOAc (90:10 to 80:20)

Sources & evidence

ORD record
ord-2bffd9e2d85942cbb70d04b1477d6fef
Source dataset
uspto-grants-2016_05
Patent number
US09340503B2

Reaction notes

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