Dimethylformamide → 6-Methoxypyridine-3-carbaldehyde

HRID 488810Notes

Reaction equation

HRID 488810 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[Li]CCCC.CN([CH:18]=[O:19])C.[NH4+].[Cl-]>CCOCC>[CH3:9][O:8][C:5]1[CH:4]=[CH:3][C:2]([CH:18]=[O:19])=[CH:7][N:6]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 27348955-Bromo-2-methoxypyridineHCID 178418339Butyllithium

Product 1

HCID 33645766-Methoxypyridine-3-carbaldehyde

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-64 °C

Procedure

To a solution of 5-bromo-2-methoxy-pyridine (8.50 g, 45.2 mmol) in 100 mL dry ether under argon at −64° C. was added 1.6 M n-BuLi in hexanes. The resulting mixture was stirred at −64° C. for 40 minutes and allowed to warm to −35° C. To the resulting suspension was added 7.0 mL of dry DMF over 10 minutes. After 15 minutes, the mixture was allowed to warm to 0° C. and 75 mL of 5% NH4Cl was added. The resulting mixture was separated and the aqueous layer extracted with EtOAc (3×75 mL). The organics were combined, dried (MgSO4), filtered and evaporated under vacuum to give 2-methoxy-pyridine-5-carboxaldehyde as a tannish solid (recrystallized from hexane), 3.76 g (60.6%); m.p. 48.5-50° C.

Workup

  1. temperatureto warm to −35° C
  2. waitAfter 15 minutes
  3. temperatureto warm to 0° C.
  4. customThe resulting mixture was separated
  5. extractionthe aqueous layer extracted with EtOAc (3×75 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated under vacuum
  9. customto give
  10. custom2-methoxy-pyridine-5-carboxaldehyde as a tannish solid (recrystallized from hexane), 3.76 g (60.6%)

Sources & evidence

ORD record
ord-b5f20d3a42754bffada595695a6007c6
Source dataset
uspto-grants-2005_12
Patent number
US06974826B2

Reaction notes

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