Dimethylformamide → N-[3-(6-Piperidinomethyl-2-pyridyloxy)propyl]formamide

HRID 370542Notes

Reaction equation

HRID 370542 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][OH:5].[H-].[Na+].Cl[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[N:10]=1.CN([CH:25]=[O:26])C>>[N:16]1([CH2:15][C:11]2[N:10]=[C:9]([O:5][CH2:4][CH2:3][CH2:2][NH:1][CH:25]=[O:26])[CH:14]=[CH:13][CH:12]=2)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

5

Reactant 4

HCID 6228Dimethylformamide2×HCID 90863-Amino-1-propanolHCID 24758Sodium hydrideHCID 133886862-Chloro-6-(piperidin-1-ylmethyl)pyridine

Product 1

HCID 13491499N-[3-(6-Piperidinomethyl-2-pyridyloxy)propyl]formamide

Procedure

3-Aminopropanol (12.84 g, 0.171 mole) was added to a suspension of 50% sodium hydride in mineral oil (7.96 g, 0.166 mole) in 180 mL of dry DMF and the mixture was warmed to 80°-83°. A solution of 2-chloro-6-piperidinomethylpyridine (34.0 g, 0.161 mole) [prepared in Step A] in 180 mL of dry DMF was then added dropwise and when complete, the temperature was raised to 125°-128° for 3 hours followed by 17 hours at ambient temperature. The precipitated salts were removed by filtration and the solvent stripped under vacuum. The oily residue was dissolved in methylene chloride, washed with water, dried and the solvent evaporated. This residue was redissolved in acetonitrile and extracted with skelly B. After removing the solvent the crude oil was purified by flash chromatography on 270 g of silica gel (230-400 mesh) using a gradient elution of methanol-methylene chloride and evaporated to give the title product as a yellow oil, 21.63 g (48.4%).

Workup

  1. temperaturethe mixture was warmed to 80°-83°
  2. temperaturewhen complete, the temperature was raised to 125°-128° for 3 hours
  3. customThe precipitated salts were removed by filtration
  4. dissolutionThe oily residue was dissolved in methylene chloride
  5. washwashed with water
  6. customdried
  7. customthe solvent evaporated
  8. dissolutionThis residue was redissolved in acetonitrile
  9. extractionextracted with skelly B
  10. customAfter removing the solvent the crude oil
  11. customwas purified by flash chromatography on 270 g of silica gel (230-400 mesh)
  12. washa gradient elution of methanol-methylene chloride
  13. customevaporated

Sources & evidence

ORD record
ord-4054b25cf4284b98a8285bb4a1684c25
Source dataset
uspto-grants-1985_07
Patent number
US04526973

Reaction notes

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