Water → N-[3-(hydroxyl-pyridin-2-yl-methyl)-pyridin-2-yl]-2,2-dimethyl-propionamide

HRID 2387217Notes

Reaction equation

HRID 2387217 reaction equation
[CH3:1]N(CCN(C)C)C.[C:9]([NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1)(=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11].[N:22]1[CH:27]=[CH:26][CH:25]=[C:24](C=O)[CH:23]=1.[OH2:30]>C(OCC)C.C1COCC1>[OH:30][CH:1]([C:27]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1)[C:21]1[C:16]([NH:15][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[N:17][CH:18]=[CH:19][CH:20]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 103713-PyridinecarboxaldehydeHCID 10515192-(Pivaloylamino)pyridine

Product 1

HCID 68632017N-[3-(hydroxyl-pyridin-2-yl-methyl)-pyridin-2-yl]-2,2-dimethyl-propionamide

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

TMEDA (2.54 ml, 16.8 mmol) is added to a solution of pivaloylamino pyridine (1 g, 5.6 mmol) in diethyl ether (40 ml), and the resulting solution is cooled to −70° C. A solution of 2.5M N-Butyl lithium in hexanes (6.73 ml, 16.8 mmol) is added dropwise to the solution, which turns a golden yellow colour. The solution is allowed to warm to −20° C. and stirred at this temperature for 2 hours. The solution is cooled to −70° C. and a solution of pyridine-3-carbaldehyde (1.16 ml, 12.3 mmol) in THF (20 ml) is added and resulting suspension is allowed to warm to room temperature and stirred overnight. H2O is added and the phases are separated, the aqueous phase is washed with DCM, and the organic phases combined, and concentrated in vacuo to afford a yellow oil. Purification by flash chromatography (SiO2, 70-100% EtOAc in iso-hexane), and drying in vacuo at 45° C. overnight yields N-[3-(hydroxyl-pyridin-2-yl-methyl)-pyridin-2-yl]-2,2-dimethyl-propionamide [M+H]+ 286.

Workup

  1. temperatureto warm to −20° C.
  2. temperatureThe solution is cooled to −70° C.
  3. customresulting suspension
  4. temperatureto warm to room temperature
  5. stirringstirred overnight
  6. customthe phases are separated
  7. washthe aqueous phase is washed with DCM
  8. concentrationconcentrated in vacuo
  9. customto afford a yellow oil
  10. customPurification by flash chromatography (SiO2, 70-100% EtOAc in iso-hexane)
  11. customdrying in vacuo at 45° C. overnight

Sources & evidence

ORD record
ord-6fea49ad59be4b1d9239152e6942f8df
Source dataset
uspto-grants-2012_09
Patent number
US08268834B2

Reaction notes

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