Sodium hydride → N-(6-(4-(benzyloxy)butoxy)-3-formylpyridin-2-yl)pivalamide

HRID 1750071Notes

Reaction equation

HRID 1750071 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][OH:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:17]1[N:22]=[C:21]([NH:23][C:24](=[O:29])[C:25]([CH3:28])([CH3:27])[CH3:26])[C:20]([CH:30]=[O:31])=[CH:19][CH:18]=1>CN(C=O)C>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:17]1[N:22]=[C:21]([NH:23][C:24](=[O:29])[C:25]([CH3:26])([CH3:27])[CH3:28])[C:20]([CH:30]=[O:31])=[CH:19][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 5622124-Benzyloxy-1-butanolHCID 14708120N-(6-chloro-3-formylpyridin-2-yl)-2,2-dimethylpropanamide

Product 1

HCID 21073962N-(6-(4-(benzyloxy)butoxy)-3-formylpyridin-2-yl)pivalamideYield 31%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(benzyloxy)butan-1-ol (15.42 g, 85.6 mmol) in DMF (120 mL) was added sodium hydride (4.11 g, 171 mmol) at 0° C. The mixture was stirred for 20 min, then intermediate 6 (10.28 g, 42.7 mmol) was added portion-wise and the resulting mixture was stirred overnight. The mixture was quenched with saturated aq NH4Cl and extracted with EtOAc. The combined organic layers were washed with water, brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography on silica gel column (elution with PE/EtOAc=8:1-4:1) to give N-(6-(4-(benzyloxy)butoxy)-3-formylpyridin-2-yl)pivalamide (intermediate 7) (5.04 g, 31%).

Workup

  1. stirringthe resulting mixture was stirred overnight
  2. customThe mixture was quenched with saturated aq NH4Cl
  3. extractionextracted with EtOAc
  4. washThe combined organic layers were washed with water, brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel column (elution with PE/EtOAc=8:1-4:1)

Sources & evidence

ORD record
ord-4ec592816d9a4b9e87ec0021402ee703
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

Loading…