Sodium hydride → 4-(3-ethoxycarbonyl-5-pyridin-4-yl-1H-pyrrol-2-yl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1400183Notes

Reaction equation

HRID 1400183 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=O)[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br.Br[CH2:26][C:27]([C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1)=O.C([O-])(=O)C.[NH4+:39]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[NH:39][C:27]([C:29]3[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=3)=[CH:26][C:15]=2[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 517165Ammonium AcetateHCID 27762394-(Bromoacetyl)pyridine hydrobromideHCID 6618868tert-Butyl 4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate

Product 1

HCID 576592924-(3-ethoxycarbonyl-5-pyridin-4-yl-1H-pyrrol-2-yl)-piperidine-1-carboxylic acid tert-butyl esterYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-(2-ethoxycarbonyl-acetyl)-piperidine-1-carboxylic acid tert-butyl ester 8 (2.5 g, 8.3 mmol) in anhydrous THF (200 mL), cooled at 0° C., NaH (900 mg, 21 mmol) was added. After 15 min 2-bromo-1-pyridin-4-yl-ethanone hydrobromide 1 (3 g, 10.8 mmol) was added and the mixture was stirred 5 h at 0° C. The solvent was removed under reduced pressure and the residue was dissolved in EtOH (120 mL). Ammonium acetate (1.9 g, 25 mmol) was added and the solution was stirred overnight at rt. After solvent removal the residue was dissolved in EtOAc and the organic phase was washed with a saturated aq solution of Na2CO3, then with water, dried (Na2SO4) and concentrated. The crude material was purified by silica gel chromatography (eluant: EtOAc) to yield 4-(3-ethoxycarbonyl-5-pyridin-4-yl-1H-pyrrol-2-yl)-piperidine-1-carboxylic acid tert-butyl ester as a pink solid (1.55 g, 47%).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in EtOH (120 mL)
  3. stirringthe solution was stirred overnight at rt
  4. customAfter solvent removal the residue
  5. dissolutionwas dissolved in EtOAc
  6. washthe organic phase was washed with a saturated aq solution of Na2CO3
  7. dry with materialwith water, dried (Na2SO4)
  8. concentrationconcentrated
  9. customThe crude material was purified by silica gel chromatography (eluant: EtOAc)

Sources & evidence

ORD record
ord-4bf57c0d154647f5964aa02e2728819d
Source dataset
uspto-grants-2014_12
Patent number
US08906934B2

Reaction notes

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