Dimethylformamide → Ethyl 5-formyl-4-methyl-1h-pyrrole-3-carboxylate

HRID 983044

Reaction equation

HRID 983044 reaction equation
O=P(Cl)(Cl)Cl.[CH2:6]([O:8][C:9]([C:11]1[C:15]([CH3:16])=[CH:14][NH:13][CH:12]=1)=[O:10])[CH3:7].[OH-].[Na+].CN([CH:22]=[O:23])C>O>[CH2:6]([O:8][C:9]([C:11]1[C:15]([CH3:16])=[C:14]([CH:22]=[O:23])[NH:13][CH:12]=1)=[O:10])[CH3:7]

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 235044Ethyl 4-methyl-1h-pyrrole-3-carboxylate

Product 1

HCID 236067Ethyl 5-formyl-4-methyl-1h-pyrrole-3-carboxylateYield 46%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

POCl3 (4 mL, 1.1 eq) added to 9 mL (3 eq) of DMF cooled in an ice bath. After 15 mins, a solution of the 4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester (6 g, 39.2 mmol) in DMF (2M, 20 mL) was added to the reaction and stirring continued at rt. After 2 hr, the reaction mixture was diluted with water (100 mL) and basified to pH=11 with 1N NaOH. The aqueous layer was extracted into DCM (2×250 mL), washing the combined organic layers with water (2×400 mL), dried (MgSO4), filtered through a plug of silica and concentrated to afford a pinkish solid. Trituration with hexanes afforded 3.3 g (46%) of 5-formyl-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester as a tan solid

Workup

  1. temperaturecooled in an ice bath
  2. customcontinued at rt
  3. waitAfter 2 hr
  4. extractionThe aqueous layer was extracted into DCM (2×250 mL)
  5. washwashing the combined organic layers with water (2×400 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered through a plug of silica
  8. concentrationconcentrated
  9. customto afford a pinkish solid

Sources & evidence

ORD record
ord-fa7d94b58410434fba39a91e301876d8
Source dataset
uspto-grants-2005_03
Patent number
US06861418B2

Linked notes

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