1,2-Dichloroethane → methyl 5-formyl-1H-pyrrole-2-carboxylate

HRID 601790Notes

Reaction equation

HRID 601790 reaction equation
ClCCCl.CN([CH:8]=[O:9])C.P(Cl)(Cl)(Cl)=O.[NH:15]1[CH:19]=[CH:18][CH:17]=[C:16]1[C:20]([O:22][CH3:23])=[O:21]>ClC(Cl)C>[CH:8]([C:19]1[NH:15][C:16]([C:20]([O:22][CH3:23])=[O:21])=[CH:17][CH:18]=1)=[O:9]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 136930Methyl pyrrole-2-carboxylate

Product 1

HCID 316531methyl 5-formyl-1H-pyrrole-2-carboxylateYield 66.5%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

To 1,2-dichloroethane (40 mL) was added DMF (13.6 mL, 176 mmol). The mixture was cooled to 0° C. and phosphorus oxychloride (16.4 mL, 176 mmol) was added dropwise over 5 min. The resulting solution was stirred for 15 min. To the solution at 0° C. was added dropwise methyl 1H-pyrrole-2-carboxylate (20 g, 160 mmol) in dichloroethane (80 mL) (about 1 h). The cooling bath was removed, and the reaction mixture was heated to reflux for about 1 h and was then cooled to rt. EtOAc (250 mL) in ice water (400 mL) was added and the organic layer was separated. The aqueous layer was neutralized with NaHCO3 solution, and then extracted with EtOAc (4×100 mL). The organic layer and the combined organic extracts were washed with dilute NaHCO3 solution, brine, dried (Na2SO4) and filtered. Silica gel was added, the solvent removed and the silica gel-imbedded material was purified by flash chromatography (0-50% EtOAc/Heptane) to afford a major product, methyl 5-formyl-1H-pyrrole-2-carboxylate (16.3 g) and a minor product, methyl 4-formyl-1H-pyrrole-2-carboxylate (6.94 g). Combined yield: 23.3 g (95%).

Workup

  1. customThe cooling bath was removed
  2. temperaturethe reaction mixture was heated
  3. temperatureto reflux for about 1 h
  4. temperaturewas then cooled to rt
  5. additionEtOAc (250 mL) in ice water (400 mL) was added
  6. customthe organic layer was separated
  7. extractionextracted with EtOAc (4×100 mL)
  8. washThe organic layer and the combined organic extracts were washed with dilute NaHCO3 solution, brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. additionSilica gel was added
  12. customthe solvent removed
  13. customthe silica gel-imbedded material was purified by flash chromatography (0-50% EtOAc/Heptane)

Sources & evidence

ORD record
ord-ea1d1057f48748d784947c3c6a797f7d
Source dataset
uspto-grants-2011_03
Patent number
US07902252B2

Reaction notes

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