Ethyl formate → Methyl 2-{1-[(ethyloxy)carbonyl]-2-hydroxyethenyl}-1-{[4-(methyloxy)phenyl]methyl}-1H-pyrrole-3-carboxylate

HRID 733740Notes

Reaction equation

HRID 733740 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1[N:7]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[CH:8]=[CH:9][C:10]=1[C:11]([O:13][CH2:14]C)=[O:12])[CH3:2].[H-].[Na+].[CH:28](OCC)=[O:29]>O1CCCC1>[CH2:1]([O:3][C:4]([C:5]([C:6]1[N:7]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[CH:8]=[CH:9][C:10]=1[C:11]([O:13][CH3:14])=[O:12])=[CH:28][OH:29])=[O:25])[CH3:2]

Participants

5

Reactant 3

HCID 8025Ethyl formateHCID 24758Sodium hydrideHCID 57841013Ethyl 2-[2-(ethyloxy)-2-oxoethyl]-1-{[4-(methyloxy)phenyl]methyl}-1H-pyrrole-3-carboxylate

Product 1

HCID 68868523Methyl 2-{1-[(ethyloxy)carbonyl]-2-hydroxyethenyl}-1-{[4-(methyloxy)phenyl]methyl}-1H-pyrrole-3-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 2-[2-(ethyloxy)-2-oxoethyl]-1-{[4-(methyloxy)phenyl]methyl}-1H-pyrrole-3-carboxylate (18.51 g) in dry tetrahydrofuran (300 ml) was stirred at room temperature under argon. Sodium hydride (60% dispersion in mineral oil, 70.0 g) was added portionwise and stirring continued for 15 minutes after complete addition. Ethyl formate (9.12 ml) was added to the reaction mixture and stirred for 30 minutes after which time an exotherm was observed and controlled by cooling the reaction mixture to room temperature with an ice bath. The reaction mixture was stirred for a further 3.5 h. The reaction mixture was cooled in an ice bath and quenched by addition of the minimum amount of methanol then evaporated. The residue was partitioned between ethyl acetate and saturated ammonium chloride, the aqueous layer was removed and acidified to pH 1 with a 2M solution of aqueous hydrochloric acid. The aqueous layer was extracted three times with ethyl acetate and the combined organic layers were washed with brine and dried (MgSO4). The solvent was evaporated to afford an oil consisting of two layers. The top layer was discarded and the lower layer isolated to afford the title compound as a brown oil (17.6 g).

Workup

  1. additionafter complete addition
  2. stirringstirred for 30 minutes after which time an exotherm
  3. stirringThe reaction mixture was stirred for a further 3.5 h
  4. temperatureThe reaction mixture was cooled in an ice bath
  5. customquenched by addition of the minimum amount of methanol
  6. customthen evaporated
  7. customThe residue was partitioned between ethyl acetate and saturated ammonium chloride
  8. customthe aqueous layer was removed
  9. extractionThe aqueous layer was extracted three times with ethyl acetate
  10. washthe combined organic layers were washed with brine
  11. dry with materialdried (MgSO4)
  12. customThe solvent was evaporated
  13. customto afford an oil
  14. customthe lower layer isolated

Sources & evidence

ORD record
ord-ad5893f6d9cd4ef29e7178786e8b3834
Source dataset
uspto-grants-2009_09
Patent number
US07589206B2

Reaction notes

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