Dimethylformamide → HCID 21071903, compound

HRID 1372418Notes

Reaction equation

HRID 1372418 reaction equation
CN(C)[CH:3]=[O:4].P(Cl)(Cl)(Cl)=O.[CH3:11][C:12]1[NH:13][CH:14]=[C:15]([CH3:26])[C:16]=1[C:17]1[CH:25]=[CH:24][C:20]([C:21]([OH:23])=[O:22])=[CH:19][CH:18]=1.[OH-].[K+]>ClCCl.O.C(OCC)(=O)C.CCCCCC.C(O)(=O)C>[CH:3]([C:14]1[NH:13][C:12]([CH3:11])=[C:16]([C:17]2[CH:25]=[CH:24][C:20]([C:21]([OH:23])=[O:22])=[CH:19][CH:18]=2)[C:15]=1[CH3:26])=[O:4]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 14797Potassium HydroxideHCID 24813Phosphorus oxychlorideHCID 21071901HCID 21071901, compound

Product 1

HCID 21071903HCID 21071903, compoundYield 50%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 21901998Ethyl acetate hexane acetic acidSolvent

Conditions

Temperature
5 °C

Procedure

Dimethylformamide (7.5 g) and 45 mL of dichloromethane were cooled to 6° C. and 7.3 mL of phosphorus oxychloride were added with stirring. 4-(2,4-Dimethyl-1H-pyrrol-3-yl)-benzoic acid (11.1 g) was slowly added. The mixture was refluxed for 30 minutes. Thin layer chromatography (ethyl acetate:hexane:acetic acid 4:6:0.5) showed no starting material at Rf 0.5 and a new spot at the origin. The mixture was cooled to 5° C. and 50 mL of ice water were added. Potassium hydroxide (9 N, 60 mL total) was slowly added with cooling. The final pH was 12–13. The maximum temperature reached was 48° C. Water (100 mL) was added along with 15 mL of dichloromethane, some of which had boiled off. The aqueous phase was isolated at a temperature of about 35° C. to prevent precipitation. The aqueous phase was adjusted to pH 3 by slow addition of about 21 mL of 10 N hydrochloric acid with stirring and cooling in an ice bath. The solids were collected by vacuum filtration and washed 3 times with 15 mL of water each time to give 5.6 g (50% yield) of 4-(5-formyl-2,4-dimethyl-1H-pyrrol-3-yl)-benzoic acid as a tan solid. 1H-NMR (dimethylsulfoxide-d6) δ 2.23, 2.27 (2×s, 2×3H, 2×CH3), 7.40, 7.95 (multiplets, 4H, aromatic), 9.56 (s, 1H, CHO), 11.85 (br s, 1H, NH), 12.90 (br s, 1H, COOH). MS m/z 244 [M+1].

Workup

  1. temperatureThe mixture was refluxed for 30 minutes
  2. temperaturewith cooling
  3. customreached was 48° C
  4. customThe aqueous phase was isolated at a temperature of about 35° C.
  5. customprecipitation
  6. additionThe aqueous phase was adjusted to pH 3 by slow addition of about 21 mL of 10 N hydrochloric acid
  7. stirringwith stirring
  8. temperaturecooling in an ice bath
  9. filtrationThe solids were collected by vacuum filtration
  10. washwashed 3 times with 15 mL of water each time

Sources & evidence

ORD record
ord-b564011661664e9abc95513e419cfec3
Source dataset
uspto-grants-2007_01
Patent number
US07157577B2

Reaction notes

Loading…