Hydrochloric Acid → ethyl 3-amino-5-[4-(ethoxycarbonyl)phenyl]-1H-pyrrole-2-carboxylate

HRID 1926024Notes

Reaction equation

HRID 1926024 reaction equation
[C:1]([CH:3]=[C:4]([C:16]1[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=1)OS(C1C=CC(C)=CC=1)(=O)=O)#[N:2].Cl.[NH2:27][CH:28](C(OCC)=O)[C:29]([O:31][CH2:32][CH3:33])=[O:30].[O-][CH2:40]C.[Na+].Cl>C(O)C.O1CCCC1>[NH2:2][C:1]1[CH:3]=[C:4]([C:16]2[CH:17]=[CH:18][C:19]([C:20]([O:22][CH2:23][CH3:40])=[O:21])=[CH:24][CH:25]=2)[NH:27][C:28]=1[C:29]([O:31][CH2:32][CH3:33])=[O:30]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 2723922Sodium ethoxideHCID 3084143Propanedioic acid, 2-amino-, 1,3-diethyl ester, hydrochloride (1:1)HCID 86615759Methyl 4-(2-cyano-1-{[(4-methylphenyl)sulfonyl]oxy}vinyl)benzoate

Product 1

HCID 67520621ethyl 3-amino-5-[4-(ethoxycarbonyl)phenyl]-1H-pyrrole-2-carboxylate

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of methyl 4-(2-cyano-1-{[(4-methylphenyl)sulfonyl]oxy}vinyl)benzoate (17.5 g) and diethyl aminomalonate hydrochloride (10.36 g) in a mixed solvent of ethanol (165 mL)-tetrahydrofuran (80 mL) was added dropwise a solution (50 mL) of 20% sodium ethoxide in ethanol under ice-cooling. After stirring under ice-cooling for 1 hr, the mixture was stirred at room temperature for 21 hr. the reaction mixture was poured into ice water (400 mL) and adjusted to pH 7 with 1N hydrochloric acid. The organic solvent was evaporated under reduced pressure, and the residue was extracted with ethyl acetate (250 mL×3). The organic layers were combined, washed with saturated brine (150 mL), and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was purified by silica gel column chromatography (eluent, hexane:ethyl acetate=2:1→1:1) and the obtained solid was recrystallized from ethyl acetate to give the title compound (4.76 g).

Workup

  1. temperaturecooling
  2. temperaturecooling for 1 hr
  3. stirringthe mixture was stirred at room temperature for 21 hr
  4. customThe organic solvent was evaporated under reduced pressure
  5. extractionthe residue was extracted with ethyl acetate (250 mL×3)
  6. washwashed with saturated brine (150 mL)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationAfter concentration under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (eluent, hexane:ethyl acetate=2:1→1:1)
  10. customthe obtained solid was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-f247aca2bfa54aee8ed9bc83774397b9
Source dataset
uspto-grants-2012_05
Patent number
US08178543B2

Reaction notes

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