Dimethylformamide → 6-Methoxypyridine-3-carbaldehyde

HRID 642858Notes

Reaction equation

HRID 642858 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.CN(C)[CH:12]=[O:13].C(=O)(O)[O-].[Na+]>O1CCCC1>[CH3:9][O:8][C:5]1[N:6]=[CH:7][C:2]([CH:12]=[O:13])=[CH:3][CH:4]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 27348955-Bromo-2-methoxypyridine

Product 1

HCID 33645766-Methoxypyridine-3-carbaldehydeYield 94.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-Butyl lithium (50 mL, 2.5M in hexane) was added drop wise to a solution of 5-Bromo-2-methoxy-pyridine (22.4 g, 119.1 mMol) in dry tetrahydrofuran (240 mL) at −78 degrees. After complete addition the solution was stirred at −78 for an additional ninety minutes at which time dimethylformamide (18.5 mL, 238.3 mMol) was added drop wise and the solution stirred for ninety more minutes at −78 and then allowed to warm to room temperature. The mixture was then poured into saturated sodium bicarbonate solution (1000 mL) and extracted with diethyl ether (3×250mL). The combined organics were dried with magnesium sulfate, filtered, and concentrated to dryness to yield 15.4 g (94% yield) of 6-Methoxy-pyridine-3-carbaldehyde as a pale yellow solid. 1H NMR (DMSO-d6): δ=9.97 (s,1H), 8.77 (m, 1H), 8.12 (dd, 1H, J=8.6, 2.3 Hz), 6.99 (d, 1H, J=8.7 Hz), 3.97 (s, 3H). LC/MS (Method A), rt=0.25 mins., purity=92.8%, calculated mass=137, [M+H]+=138. HPLC (Method C): rt=4.9 mins., purity=95.9% @ 210-370 nm and 98.7% @ 256 nm.

Workup

  1. additionAfter complete addition the solution
  2. additionwas added drop wise
  3. extractionextracted with diethyl ether (3×250mL)
  4. dry with materialThe combined organics were dried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-c56b474243844c52a773e82056be3a38
Source dataset
uspto-grants-2010_04
Patent number
US07696210B2

Reaction notes

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