Dimethylformamide → Ethyl 5-formyl-4-methyl-1H-pyrrole-2-carboxylate

HRID 1372402Notes

Reaction equation

HRID 1372402 reaction equation
P(Cl)(Cl)(Cl)=O.[CH2:6]([O:8][C:9]([C:11]1[NH:12][CH:13]=[C:14]([CH3:16])[CH:15]=1)=[O:10])[CH3:7].[OH-].[Na+].CN(C)[CH:21]=[O:22]>O>[CH2:6]([O:8][C:9]([C:11]1[NH:12][C:13]([CH:21]=[O:22])=[C:14]([CH3:16])[CH:15]=1)=[O:10])[CH3:7]

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 643361Ethyl 4-methyl-1H-pyrrole-2-carboxylate

Product 1

HCID 9855648Ethyl 5-formyl-4-methyl-1H-pyrrole-2-carboxylateYield 68%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Dimethylformamide (3 mL, 6 equivalents) was cooled with stirring in an ice bath. To this was added phosphorus oxychloride (1.1 equivalents, 0.67 mL). After 30 minutes, a solution of 4-methyl-2-pyrrolecarboxylic acid ethyl ester (1 g, 6.53 mmol) in dimethylformamide (2M, 3 mL) was added to the reaction and stirring continued. After 1 hour, the reaction was warmed to room temperature. After another 2.5 hours, the reaction mixture was diluted with water (100 mL) and basified to pH 11 with 1 N sodium hydroxide solution. The precipitate was collected by vacuum filtration, washed with water and dried to afford 0.8 g (68% yield) 5-formyl-4-methyl-1H-pyrrole-2-carboxylic acid ethyl ester as a white solid. 1H-NMR (360 MHz, dimethylsulfoxide-d6) δ 12.6 (br s, 1H, NH), 9.78 (s, 1H, CHO), 6.68 (s, 1H, CH), 4.26 (q, 2H, OCH2), 2.28 (s, 3H, CH3), 1.28 (t, 3H, CH3). MS m/z 181 [M+].

Workup

  1. stirringstirring
  2. waitAfter 1 hour
  3. waitAfter another 2.5 hours
  4. filtrationThe precipitate was collected by vacuum filtration
  5. washwashed with water
  6. customdried

Sources & evidence

ORD record
ord-d1e829ccac5c472eb9e987841e0bf023
Source dataset
uspto-grants-2007_01
Patent number
US07157577B2

Reaction notes

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