Dimethylformamide → ethyl 5-formyl-1H-pyrrole-2-carboxylate

HRID 32881

Reaction equation

HRID 32881 reaction equation
CN([CH:4]=[O:5])C.P(Cl)(Cl)(Cl)=O.[NH:11]1[CH:15]=[CH:14][CH:13]=[C:12]1[C:16]([O:18][CH2:19][CH3:20])=[O:17].C(=O)(O)[O-].[Na+]>ClCCCl.O.C(OCC)(=O)C>[CH2:19]([O:18][C:16]([C:12]1[NH:11][C:15]([CH:4]=[O:5])=[CH:14][CH:13]=1)=[O:17])[CH3:20]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 255670Ethyl 1H-pyrrole-2-carboxylateHCID 516892Sodium Bicarbonate

Product 1

HCID 321485ethyl 5-formyl-1H-pyrrole-2-carboxylateYield 42%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolvent2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

To DMF (1.3 mL, 17 mmol) cooled to 5-10° C. was added phosphorous oxychloride (1.5 mL) dropwise and the mixture was diluted with 1,2-dichloroethane (5 mL). The flask was then cooled to −10° C. and ethyl pyrrole-2-carboxylate (2.00 g, 14.4 mmol) in 1,2-dichloroethane (5 mL) was added dropwise over 5 min. The mixture was heated to reflux for 15 min, cooled to RT and ethyl acetate (15 mL), water (20 mL), and satd aq sodium bicarbonate (70 mL) were added. The layers were separated and the aqueous layer was extracted with diethyl ether (3×20 mL). The combined organic layers were washed with saturated sodium carbonate (50 mL), dried (Na2SO4) and the solvents were removed in vacuo. The resulting solid was purified by column chromatography on silica gel (300 g), eluting with 30% ethyl acetate in hexane to yield 1.0 g (42%) of the title compound as a pale yellow crystalline solid. 1H-NMR (400 MHz, CDCl3): δ 9.89 (br s, 1H), 9.67 (s, 1H), 6.95 (d, 1H, J=4.1 Hz), 6.94 (d, 1H, J=4.1 Hz), 4.38 (q, 2H, J=7.1 Hz), 1.39 (t, 3H, J=7.1).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 15 min
  3. temperaturecooled to RT
  4. additionwere added
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with diethyl ether (3×20 mL)
  7. washThe combined organic layers were washed with saturated sodium carbonate (50 mL)
  8. dry with materialdried (Na2SO4)
  9. customthe solvents were removed in vacuo
  10. customThe resulting solid was purified by column chromatography on silica gel (300 g)
  11. washeluting with 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-6c517d500b9b40f7bc2a95216b3c019a
Source dataset
uspto-grants-2008_09
Patent number
US07427683B2

Linked notes

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