Dimethylformamide → N-(3-formylpyridin-4-yl)-2,2-dimethylpropanamide

HRID 2307768Notes

Reaction equation

HRID 2307768 reaction equation
[CH3:1][C:2]([CH3:13])([CH3:12])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][N:9]=[CH:8][CH:7]=1)=[O:4].[Li]CCCC.CN([CH:22]=[O:23])C>C1COCC1.[Cl-].[Na+].O>[CH:22]([C:7]1[CH:8]=[N:9][CH:10]=[CH:11][C:6]=1[NH:5][C:3](=[O:4])[C:2]([CH3:13])([CH3:12])[CH3:1])=[O:23]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 4270594-(2,2,2-Trimethylacetamido)pyridineHCID 178418339Butyllithium

Product 1

HCID 2779664N-(3-formylpyridin-4-yl)-2,2-dimethylpropanamideYield 69%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of Example 25A (11.4 g, 64 mmol) in 200 mL THF was cooled to −78° C., treated with 1.6 M nBuLi in hexanes (100 mL, 160 mmol), warmed to 0° C., stirred for 1 hour, treated with a solution of DMF (22 g, 215 mmol) in 100 mL THF, warmed to room temperature, stirred for 1 hour, diluted with brine, and extracted three times with ethyl acetate. The combined extracts were washed with water, washed twice with brine, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 3% methanol/dichloromethane to provide the desired product (9.1 g, 69%).

Workup

  1. temperaturewarmed to room temperature
  2. stirringstirred for 1 hour
  3. extractionextracted three times with ethyl acetate
  4. washThe combined extracts were washed with water
  5. washwashed twice with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe concentrate was purified by flash column chromatography on silica gel with 3% methanol/dichloromethane

Sources & evidence

ORD record
ord-76bde00c3a744a968cfd6e687dec3257
Source dataset
uspto-grants-2004_12
Patent number
US06831175B2

Reaction notes

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