Sodium hydride → 2-cyclohexyl-5-pyridin-4-yl-1H-pyrrole-3-carboxylic acid ethyl ester
Reaction equation
[CH2:1]([O:3][C:4](=[O:14])[CH2:5][C:6]([CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)=O)[CH3:2].[H-].[Na+].Br.Br[CH2:19][C:20]([C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1)=O.C([O-])(=O)C.[NH4+:32]>C1COCC1>[CH2:1]([O:3][C:4]([C:5]1[CH:19]=[C:20]([C:22]2[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=2)[NH:32][C:6]=1[CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:14])[CH3:2]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a solution of 3-cyclohexyl-3-oxo-propionic acid ethyl ester 5 (1.6 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 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 aqueous solution of Na2CO3, then with water, dried (Na2SO4) and concentrated. The crude material was purified by silica gel chromatography (eluant: EtOAc) to yield 2-cyclohexyl-5-pyridin-4-yl-1H-pyrrole-3-carboxylic acid ethyl ester as a white solid (1.1 g, 43%).
Workup
- customThe solvent was removed
- dissolutionthe residue was dissolved in EtOH (120 mL)
- stirringthe solution was stirred overnight at rt
- customAfter solvent removal the residue
- dissolutionwas dissolved in EtOAc
- washthe organic phase was washed with a saturated aqueous solution of Na2CO3
- dry with materialwith water, dried (Na2SO4)
- concentrationconcentrated
- customThe crude material was purified by silica gel chromatography (eluant: EtOAc)
Sources & evidence
- ORD record
- ord-0bd6b49508bb40ee927ec3a385139b08
- Source dataset
- uspto-grants-2015_06
- Patent number
- US09056854B2
Reaction notes
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