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

HRID 2375795Notes

Reaction equation

HRID 2375795 reaction equation
CN([CH:4]=[O:5])C.O=P(Cl)(Cl)Cl.[CH2:11]([O:18][C:19]([C:21]1[NH:22][CH:23]=[CH:24][CH:25]=1)=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[C:26]([O-])(=[O:28])C.[Na+]>C(Cl)Cl.O>[CH2:11]([O:18][C:19]([C:21]1[NH:22][C:23]([CH:4]=[O:5])=[CH:24][CH:25]=1)=[O:20])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1.[CH2:11]([O:18][C:19]([C:21]1[NH:22][CH:23]=[C:24]([CH:26]=[O:28])[CH:25]=1)=[O:20])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 517045Sodium AcetateHCID 8543774HCID 8543774, compound

Product 2

HCID 71349636Benzyl 5-formyl-1H-pyrrole-2-carboxylateHCID 84103256185621-28-7

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To DMF (5.93 g) was added POCl3 (12.45 g) dropwise at 0° C. The mixture was warmed to RT, diluted with DCM (40 mL) and cooled again to 0° C. A solution of 1H-pyrrole-2-carboxylic acid benzyl ester (15.00 g, prepared by adopting a procedure from J. Barry, G. Bram and A. Petit, Heterocycles 1985, 23, 875-880) in DCM (40 mL) was added dropwise at such a rate that the temperature of the reaction mixture did not rise above 0° C. The reaction was the heated to reflux for 30 min whereupon it was cooled to 10° C. A solution of sodium acetate (28g) in water (90 mL) was added carefully. After stirring for 15 min the two resulting phases were separated and the aqueous phase was washed with DCM (3×75 mL). The combined organic phases were washed with saturated Na2CO3 solution and brine, dried over MgSO4 and concentrated. The residue was purified by flash column chromatography on silica (ethyl acetate/heptanes 1:2) to provide 5-formyl-1H-pyrrole-2-carboxylic acid benzyl ester (8.0 g) and 4-formyl-1H-pyrrole-2-carboxylic acid benzyl ester (4.0 g).

Workup

  1. temperaturecooled again to 0° C
  2. customdid not rise above 0° C
  3. temperatureheated
  4. temperatureto reflux for 30 min whereupon it
  5. temperaturewas cooled to 10° C
  6. customwere separated
  7. washthe aqueous phase was washed with DCM (3×75 mL)
  8. washThe combined organic phases were washed with saturated Na2CO3 solution and brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated
  11. customThe residue was purified by flash column chromatography on silica (ethyl acetate/heptanes 1:2)

Sources & evidence

ORD record
ord-1f1278a2b66443fe9b0921c9123a3755
Source dataset
uspto-grants-2008_12
Patent number
US07465806B2

Reaction notes

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