Sodium Acetate → tert-butyl 4-[4-amino-5-(ethoxycarbonyl)-1H-pyrrol-3-yl]piperidine-1-carboxylate

HRID 1616086Notes

Reaction equation

HRID 1616086 reaction equation
[C:1]([CH:3]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)[CH:4]=O)#[N:2].Cl.[NH2:20][CH:21](C(OCC)=O)[C:22]([O:24][CH2:25][CH3:26])=[O:23].C([O-])(=O)C.[Na+].[O-]CC.[Na+]>CO.O>[NH2:2][C:1]1[C:3]([CH:6]2[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]2)=[CH:4][NH:20][C:21]=1[C:22]([O:24][CH2:25][CH3:26])=[O:23]

Participants

7

Reactant 4

HCID 517045Sodium AcetateHCID 2723922Sodium ethoxideHCID 3084143Propanedioic acid, 2-amino-, 1,3-diethyl ester, hydrochloride (1:1)HCID 86681870Tert-butyl 4-(1-cyano-2-oxoethyl)piperidine-1-carboxylate

Product 1

HCID 86681878tert-butyl 4-[4-amino-5-(ethoxycarbonyl)-1H-pyrrol-3-yl]piperidine-1-carboxylateYield 46%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

The tert-butyl 4-(1-cyano-2-oxoethyl)piperidine-1-carboxylate (757 mg, 3.0 mmol) obtained in Step 4 of Example 1 was dissolved in methanol (6 mL) and water (2 mL), diethyl aminomalonate hydrochloride (952 mg, 4.5 mmol) and sodium acetate (492 mg, 6.0 mmol) were added, followed by stirring at room temperature for 18 hours. The reaction liquid was concentrated under a reduced pressure and dissolved in chloroform. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under a reduced pressure. The obtained residue (1.53 g) was dissolved in ethanol (6 mL), and then sodium ethoxide (510 mg, 7.5 mmol) was added, followed by heating under reflux for 3 hours. The reaction liquid was concentrated under a reduced pressure, and the obtained residue was dissolved in ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under a reduced pressure. The obtained residue was purified by using silica gel chromatography (chloroform:methanol=100:1→50:1) to give tert-butyl 4-[4-amino-5-(ethoxycarbonyl)-1H-pyrrol-3-yl]piperidine-1-carboxylate (466 mg, 46.0%) as a pale yellow amorphous.

Workup

  1. customThe reaction liquid
  2. concentrationwas concentrated under a reduced pressure
  3. dissolutiondissolved in chloroform
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under a reduced pressure
  7. dissolutionThe obtained residue (1.53 g) was dissolved in ethanol (6 mL)
  8. temperatureby heating
  9. temperatureunder reflux for 3 hours
  10. customThe reaction liquid
  11. concentrationwas concentrated under a reduced pressure
  12. dissolutionthe obtained residue was dissolved in ethyl acetate
  13. washThe organic layer was washed with saturated brine
  14. dry with materialdried over anhydrous sodium sulfate
  15. concentrationconcentrated under a reduced pressure
  16. customThe obtained residue was purified

Sources & evidence

ORD record
ord-2599562d154e47768b1e1de0c5f93256
Source dataset
uspto-grants-2014_07
Patent number
US08765771B2

Reaction notes

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