Hydrochloric Acid → N-(3-formyl-4-methylpyridin-2-yl)-2,2-dimethylpropanamide

HRID 987901Notes

Reaction equation

HRID 987901 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])[CH:3]=1.[Li]C(C)(C)C.CN([CH:23]=[O:24])C.Cl.C([O-])([O-])=O.[K+].[K+]>C(OCC)C>[CH:23]([C:3]1[C:4]([NH:8][C:9](=[O:14])[C:10]([CH3:11])([CH3:13])[CH3:12])=[N:5][CH:6]=[CH:7][C:2]=1[CH3:1])=[O:24]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 35314852,2-Dimethyl-N-(4-Methyl-2-pyridyl)propionamideHCID 178418306HCID 178418306, compound

Product 1

HCID 22987126N-(3-formyl-4-methylpyridin-2-yl)-2,2-dimethylpropanamideYield 59%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

To a precooled (−78° C.) solution of 4-methyl-2-(pivaloylamino)pyridine (6.87 g, 36.0 mmol) in diethyl ether (100 mL, dried over molecular seives) was slowly added tert-BuLi (50.0 mL, 75.0 mmol). The resulting solution was stirred at −78° C. for 3.5 h prior to the addition of DMF (5.19 g, 71.0 mmol) and was stirred for additionally 30 min at −78° C. and then allowed to warm to rt, and poored into 2 M HCl (aqueous, 100 mL). After stirring this mixture for 15 min. the pH was adjusted to 7.0 by addition of K2CO3. The aqueous phase washed with diethyl ether (3×75 mL, dried over molecular seives), and the combined organic fractions was washed with brine (100 mL), dried (MgSO4) and evaporated in vacuo. The crude product was recrystallised from ethyl acetate/hexane to give the desired product (4.66 g, 59%) as a slightly tan crystals (mp 117-20° C.). 1H NMR(DMSO-d6): δ 11.19 (s br, 1H), 10.41 (s, 1H), 8.49 (d, 5.0 Hz, 1H), 6.92 (d, 5.0 Hz), 2.69 (s, 3H), 1.37 (s, 9H). 13C NMR (DMSO-d6): δ 192.02, 176.97, 154.15, 152.82, 152.69, 121.70, 116.09, 40.69, 27.46, 18.77. FAB+ MS (m/z): 221.1300 (M+H+, calc. for C12H16N2O2+H+ 221.1290).

Workup

  1. stirringwas stirred for additionally 30 min at −78° C.
  2. temperatureto warm to rt
  3. stirringAfter stirring this mixture for 15 min. the pH
  4. washThe aqueous phase washed with diethyl ether (3×75 mL, dried over molecular seives)
  5. washthe combined organic fractions was washed with brine (100 mL)
  6. dry with materialdried (MgSO4)
  7. customevaporated in vacuo
  8. customThe crude product was recrystallised from ethyl acetate/hexane

Sources & evidence

ORD record
ord-2546935636d54aac91a0d8a490446b0e
Source dataset
uspto-grants-2003_10
Patent number
US06632919B1

Reaction notes

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