Sodium hydride → N-(6-Cyclopropylmethoxymethyl-pyridin-2-yl)-2,2-dimethyl-propionamide

HRID 1454820Notes

Reaction equation

HRID 1454820 reaction equation
[OH:1][CH2:2][C:3]1[N:8]=[C:7]([NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])[CH:6]=[CH:5][CH:4]=1.[H-].[Na+].Br[CH2:19][CH:20]1[CH2:22][CH2:21]1>CN(C=O)C>[CH:20]1([CH2:19][O:1][CH2:2][C:3]2[N:8]=[C:7]([NH:9][C:10](=[O:15])[C:11]([CH3:12])([CH3:14])[CH3:13])[CH:6]=[CH:5][CH:4]=2)[CH2:22][CH2:21]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 21782926N-[6-(Hydroxymethyl)pyridin-2-yl]-2,2-dimethylpropanamide

Product 1

HCID 68842943N-(6-Cyclopropylmethoxymethyl-pyridin-2-yl)-2,2-dimethyl-propionamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-(6-Hydroxymethyl-pyridin-2-yl)-2,2-dimethyl-propionamide (1.04 g, Papadopoulou,; J. Heterocycl. Chem., 32, 1995, 675) in DMF (25 mL) was treated with sodium hydride (0.64 g, 60% suspension in oil), the mixture was then stirred for 1 h at RT, bromomethyl cyclopropane (0.688 g) was added dropwise and stirring was continued for further 1.75 h. The reaction mixture was partitioned between 2 M aqueous KHCO3 and AcOEt, the layers were separated, the aqueous layer extracted twice with AcOEt. The combined organic layers were washed with saturated aqueous NaCl and water, dried over Na2SO4, filtered and evaporated. The residue was purified by flash chromatography (heptane/AcOEt 100% to 50%) to N-(6-cyclopropylmethoxymethyl-pyridin-2-yl)-2,2-dimethyl-propionamide (0.884 g) as a yellow oil. MS (ESI): 263.2 (MH+).

Workup

  1. stirringstirring
  2. waitwas continued for further 1.75 h
  3. customThe reaction mixture was partitioned between 2 M aqueous KHCO3 and AcOEt
  4. customthe layers were separated
  5. extractionthe aqueous layer extracted twice with AcOEt
  6. washThe combined organic layers were washed with saturated aqueous NaCl and water
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by flash chromatography (heptane/AcOEt 100% to 50%) to N-(6-cyclopropylmethoxymethyl-pyridin-2-yl)-2,2-dimethyl-propionamide (0.884 g) as a yellow oil

Sources & evidence

ORD record
ord-ee0504186ddc4fb99c858fd96d322870
Source dataset
uspto-grants-2009_01
Patent number
US07482341B2

Reaction notes

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