Hydrochloric Acid → 2-[3-cyano-4-(1H-pyrrol-1-yl)phenyl]isonicotinic acid

HRID 562924Notes

Reaction equation

HRID 562924 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:14]2[CH:15]=[C:16]([CH:21]=[CH:22][N:23]=2)[C:17]([O:19]C)=[O:18])[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[CH:12][CH:11]=[CH:10]1)#[N:2].Cl>CO.C1COCC1.[OH-].[Na+]>[C:1]([C:3]1[CH:4]=[C:5]([C:14]2[CH:15]=[C:16]([CH:21]=[CH:22][N:23]=2)[C:17]([OH:19])=[O:18])[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[CH:12][CH:11]=[CH:10]1)#[N:2]

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 66995160methyl 2-[3-cyano-4-(1H-pyrrol-1-yl)phenyl]isonicotinate

Product 1

HCID 669954272-[3-cyano-4-(1H-pyrrol-1-yl)phenyl]isonicotinic acidYield 99.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

131 mg of methyl 2-(4-amino-3-cyanophenyl)isonicotinate and 67 μl of 2,5-dimethoxytetrahydrofuran were dissolved in 1.3 ml of acetic acid solution, followed by heating and stirring at 100° C. for 4 hours. The solution was poured into water, followed by extraction with ethyl acetate. The solvent of the organic layer was evaporated under reduced pressure, and the residue was purified by column chromatography (hexane:ethyl acetate=10:1 to 1:1) to obtain 100 mg of methyl 2-[3-cyano-4-(1H-pyrrol-1-yl)phenyl]isonicotinate. (2) 100 mg of methyl 2-[3-cyano-4-(1H-pyrrol-1-yl)phenyl]isonicotinate was dissolved in a mixture of 2 ml of methanol and 3 ml of THF, and 66 μl of aqueous 1 M sodium hydroxide solution was added, followed by heating under reflux for 3 hours. The reaction mixture was cooled, then neutralized with 66 μl of 1 M hydrochloric acid, followed by extraction with a mixture of 2-propanol and chloroform (1:4). The organic layer was washed with brine. The solvent of the organic layer was evaporated under reduced pressure, and the resulting residue was recrystallized from a mixture of 2-propanol and chloroform (1:4) to obtain 95 mg of 2-[3-cyano-4-(1H-pyrrol-1-yl)phenyl]isonicotinic acid.

Workup

  1. additionwas added
  2. temperatureby heating
  3. temperatureunder reflux for 3 hours
  4. temperatureThe reaction mixture was cooled
  5. extractionfollowed by extraction with a mixture of 2-propanol and chloroform (1:4)
  6. washThe organic layer was washed with brine
  7. customThe solvent of the organic layer was evaporated under reduced pressure
  8. customthe resulting residue was recrystallized from a mixture of 2-propanol and chloroform (1:4)

Sources & evidence

ORD record
ord-07c99c7a17c841ee9676c6b47c2ec37a
Source dataset
uspto-grants-2011_11
Patent number
US08067446B2

Reaction notes

Loading…