Dimethylformamide → 2-(5-Formyl-2,4-dimethyl-1H-pyrrol-3-YL)acetic acid

HRID 1372388Notes

Reaction equation

HRID 1372388 reaction equation
CN(C)[CH:3]=[O:4].ClCCl.P(Cl)(Cl)(Cl)=O.[CH3:14][C:15]1[NH:16][CH:17]=[C:18]([CH3:24])[C:19]=1[CH2:20][C:21]([OH:23])=[O:22]>C(OCC)(=O)C.CCCCCC.C(O)(=O)C>[CH:3]([C:17]1[NH:16][C:15]([CH3:14])=[C:19]([CH2:20][C:21]([OH:23])=[O:22])[C:18]=1[CH3:24])=[O:4]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6344DichloromethaneHCID 24813Phosphorus oxychlorideHCID 21071878HCID 21071878, compound

Product 1

HCID 221354182-(5-Formyl-2,4-dimethyl-1H-pyrrol-3-YL)acetic acidYield 96.3%

Reagents, catalysts & solvents 1

HCID 21901998Ethyl acetate hexane acetic acidSolvent

Conditions

Temperature
20 °C

Procedure

Dimethylformamide (230 mL, 3.13 mol) and 1200 mL of dichloromethane were cooled to 4° C. and 222 mL of phosphorus oxychloride was added with stirring. The temperature increased to 20° C. The mixture was cooled to 2° C. (2,4-Dimethyl-1H-pyrrol-3-yl)-acetic acid (240 g, 1.57 mol) was slowly added. The mixture was refluxed for 20 minutes. Thin layer chromatography (ethyl acetate:hexane:acetic acid 4:6:0.5) showed no starting material at Rf 0.7 and a heavy spot at the origin. The mixture was cooled to 5° C. and 1200 mL of ice water were added. The maximum temperature reached was 30° C. The mixture was stirred in an ice bath for 30 minutes. The dichloromethane layer was separated and discarded. The aqueous layer was cooled to 9° C. and adjusted to pH 12 with about 1650 mL of 9 N potassium hydroxide. The maximum temperature reached was 50° C. The mixture was cooled in an ice bath and adjusted to pH 3 with about 800 mL of 10 N hydrochloric acid. The solids were collected by vacuum filtration, washed three times with 300 mL of water each time and air dried to give 274 g (96% yield) of (5-formyl-2,4-dimethyl-1H-pyrrol-3-yl)-acetic acid as a brown solid. 1H-NMR (dimethylsulfoxide-d6) δ 2.15, 2.18 (2×s, 2×3H, 2×CH3), 3.28 (s, 2H, CH2), 9.44 (s, 1H, CHO), 11.50 (s, 1H, pyrrole NH), 12.07 (s, 1H, COOH). MS m/z 182, [M+1].

Workup

  1. additionwas slowly added
  2. temperatureThe mixture was refluxed for 20 minutes
  3. temperatureThe mixture was cooled to 5° C.
  4. customreached was 30° C
  5. stirringThe mixture was stirred in an ice bath for 30 minutes
  6. customThe dichloromethane layer was separated
  7. temperatureThe aqueous layer was cooled to 9° C.
  8. customreached was 50° C
  9. temperatureThe mixture was cooled in an ice bath
  10. filtrationThe solids were collected by vacuum filtration
  11. washwashed three times with 300 mL of water each time and air
  12. customdried

Sources & evidence

ORD record
ord-bb4cf07e3e954ff0a10ef9d62538064b
Source dataset
uspto-grants-2007_01
Patent number
US07157577B2

Reaction notes

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