Hydrochloric Acid → N-(4-Formyl-pyridin-3-yl)-2,2-dimethyl-propionamide

HRID 605004

Reaction equation

HRID 605004 reaction equation
[CH3:1][C:2]([CH3:13])([CH3:12])[C:3]([NH:5][C:6]1[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=1)=[O:4].C([Li])CCC.CCCCCC.CN(C)[CH:27]=[O:28].Cl>O1CCCC1>[CH:27]([C:11]1[CH:10]=[CH:9][N:8]=[CH:7][C:6]=1[NH:5][C:3](=[O:4])[C:2]([CH3:13])([CH3:12])[CH3:1])=[O:28]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 46550442,2-dimethyl-N-(pyridin-3-yl)propanamideHCID 178418244HCID 178418244, compound

Product 1

HCID 1519484N-(4-Formyl-pyridin-3-yl)-2,2-dimethyl-propionamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

A solution of 2,2-dimethyl-N-(3-pyridinyl)propanamide (3.56 gm, 20 mmol) (prepared as described in J. Org. Chem. 48, 3401 (1983)) in anhydrous tetrahydrofuran (40 mL) was cooled to −70° C. and a solution of 2.5 M n-butyl lithium/hexane (20 mL, 50 mmol) was added dropwise maintaining the temperature at −70° C. This reaction was slowly warmed to −5° C. giving a copious precipitate. This mixture was cooled to −70° C. and dry dimethyl formamide (4.64 mL, 60 mmol) was added. The reaction was allowed to warm to room temperature giving a clear yellow solution. This reaction was poured into 8 N aqueous HCl (16 mL) and ice. After stirring for 10 minutes the pH of the solution was adjusted to 7 and extracted with diethyl ether. The organic layer was dried (Na2SO4), filtered and the solvent evaporated. The residue was purified by column chromatography eluting with 30-100% ethyl acetate/hexane. The appropriate fractions were combined and the solvent removed in vacuo to give the title compound as a solid. 1H-NMR (500 MHz, CDCl3): δ 10.92 (1H, br s), 10.15 (1H, s), 10.05 (1H, s), 8.62 (2H, d, J=4.9 Hz), 7.56 (1H, d, J=4.9 Hz),), 1.39 (9H, s). m/e (m+1): 235.3.

Workup

  1. temperatureThis reaction was slowly warmed to −5° C.
  2. customgiving a copious precipitate
  3. temperatureThis mixture was cooled to −70° C.
  4. temperatureto warm to room temperature
  5. customgiving a clear yellow solution
  6. extractionextracted with diethyl ether
  7. dry with materialThe organic layer was dried (Na2SO4)
  8. filtrationfiltered
  9. customthe solvent evaporated
  10. customThe residue was purified by column chromatography
  11. washeluting with 30-100% ethyl acetate/hexane
  12. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-5ea91fc4321245949cd986a6908d3b2d
Source dataset
uspto-grants-2011_03
Patent number
US07910561B2

Linked notes

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