Nitrogen → HCID 11665798, compound

HRID 1821721Notes

Reaction equation

HRID 1821721 reaction equation
C(C1C(CC(N)=O)=C2N(C=1)C=CC=C2)C.C(Cl)(=O)CC.N#N.[CH2:23]([C:25]1[C:26]([CH2:38][C:39]([NH2:41])=O)=[C:27]2[N:32]([C:33]=1[C:34](=O)[CH2:35][CH3:36])[CH:31]=[CH:30][CH:29]=[CH:28]2)[CH3:24].[H-].[Al+3].[Li+].[H-].[H-].[H-]>ClC(Cl)C.C(OCC)C.C(N(CC)CC)C>[CH2:23]([C:25]1[C:26]([CH2:38][CH2:39][NH2:41])=[C:27]2[N:32]([C:33]=1[CH2:34][CH2:35][CH3:36])[CH:31]=[CH:30][CH:29]=[CH:28]2)[CH3:24]

Participants

9

Reactant 5

HCID 947Nitrogen2×HCID 62324Propionyl chlorideHCID 21226445Aluminium lithium hydrideHCID 68981131HCID 68981131, compoundHCID 68983124HCID 68983124, compound

Product 1

HCID 11665798HCID 11665798, compound

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 63651,1-DichloroethaneSolventHCID 8471TriethylamineSolvent

Procedure

2-(2-ethylindolizin-1-yl)acetamide (1.0 g, 5 mmol) was dissolved in dichloroethane (30 mL) to which was added triethylamine (TEA, 0.65 mL) N,N-dimethylaminopyridine (DMAP, 60 mg) and propionyl chloride (0.7 mL). The reaction mixture was heated under reflux in a N2 atmosphere overnight. The cooled reaction mixture was partitioned between water and methylene chloride. The phases were separated and the aqueous phase was extracted with methylene chloride 3 times. The organic layers were combined and evaporated to give a residue which was purified by silica gel column chromatography eluting with ethyl acetate. A total of 600 mg of 2-(2-ethyl-3-propionylindolizin-1-yl)-acetamide was recovered. 2-(2-ethyl-3-propionylindolizin-1-yl)-acetamide (400 mg, 1.5 mmol) was suspended in anhydrous ethyl ether to which lithium aluminum hydride (LAH, 380 mg) was added. The suspension was heated under reflux in a N2 atmosphere overnight. After cooling to room temperature the reaction mixture was partitioned between ether and aqueous Rochelle salt. After stirring for 1 h, the phases were separated. The aqueous phase was extracted with ether 2 times. Evaporation of the combined organic layers gave a residue which was purified on silica gel eluting with 1 L each of 5%, 10%, 12% methanol in methylene chloride containing 4 mL of conc. NH4OH. The title compound was isolated (85 mg), dissolved in ethanol and treated with an ethanolic solution of fumaric acid (65 mg). The ethanol was evaporated and the residue was recrystallized from methyl ethyl ketone (MEK) to give the title compound as the fumaric acid salt, mp: 154-158° C.; Mass sSpectrum [M+H]+ 231 m/z.

Workup

  1. temperatureThe reaction mixture was heated
  2. customThe cooled reaction mixture
  3. customwas partitioned between water and methylene chloride
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted with methylene chloride 3 times
  6. customevaporated
  7. customto give a residue which
  8. customwas purified by silica gel column chromatography
  9. washeluting with ethyl acetate
  10. customA total of 600 mg of 2-(2-ethyl-3-propionylindolizin-1-yl)-acetamide was recovered
  11. additionwas added
  12. temperatureThe suspension was heated
  13. customwas partitioned between ether and aqueous Rochelle salt
  14. customthe phases were separated
  15. extractionThe aqueous phase was extracted with ether 2 times
  16. customEvaporation of the combined organic layers
  17. customgave a residue which
  18. customwas purified on silica gel eluting with 1 L each of 5%, 10%, 12% methanol in methylene chloride containing 4 mL of conc. NH4OH

Sources & evidence

ORD record
ord-15df839be2164a9ea8facb9ddd87f034
Source dataset
uspto-grants-2009_10
Patent number
US07608626B2

Reaction notes

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