Sodium Hydroxide → 6-(6-Methoxy-2-thiophen-3-yl-1H-indol-3-ylmethyl)pyridine-2-carboxylic acid

HRID 2409945Notes

Reaction equation

HRID 2409945 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH2:17][C:18]3[N:23]=[C:22]([C:24]([O:26]C)=[O:25])[CH:21]=[CH:20][CH:19]=3)=[C:8]([C:12]3[CH:16]=[CH:15][S:14][CH:13]=3)[NH:9]2)=[CH:5][CH:4]=1.[OH-].[Na+]>O1CCCC1.CO>[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH2:17][C:18]3[N:23]=[C:22]([C:24]([OH:26])=[O:25])[CH:21]=[CH:20][CH:19]=3)=[C:8]([C:12]3[CH:16]=[CH:15][S:14][CH:13]=3)[NH:9]2)=[CH:5][CH:4]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86703270Methyl 6-(6-methoxy-2-thiophen-3-yl-1H-indol-3-ylmethyl)pyridine-2-carboxylate

Product 1

HCID 509020026-(6-Methoxy-2-thiophen-3-yl-1H-indol-3-ylmethyl)pyridine-2-carboxylic acidYield 60.7%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of methyl 6-(6-methoxy-2-thiophen-3-yl-1H-indol-3-ylmethyl)pyridine-2-carboxylate (936 mg) in tetrahydrofuran/methanol (14.7 mL/6.3 mL) was added 2 mol/L aqueous sodium hydroxide solution (3.71 mL) at room temperature, and this mixture was stirred at 60° C. for 2 hours. The reaction mixture was left to be cooled and concentrated under reduced pressure. The residue was suspended in water (30 mL) and the resulting mixture was acidified by the addition of 1 mol/L hydrochloric acid (7.8 mL). After stirring at room temperature for 1 hour, the precipitate was collected by filtration, washed with water, and then dried under reduced pressure. The suspension of the solid in ethanol was heated under reflux to give a solution. The solution was left to be cooled. The precipitate was collected by filtration and dried under reduced pressure to obtain the title compound (547 mg). 1H-NMR (DMSO-d6) δ ppm: 3.77 (3H, s), 4.37 (2H, s), 6.64 (1H, dd, J=2.3, 8.8 Hz), 6.85 (1H, d, J=2.3 Hz), 7.37 (1H, dd, J=1.5, 7.3 Hz), 7.42 (1H, d, J=8.8 Hz), 7.57 (1H, dd, J=1.3, 5.0 Hz), 7.67 (1H, dd, J=2.8, 5.0 Hz), 7.77-7.88 (2H, m), 8.09 (1H, dd, J=1.3, 2.8 Hz), 11.13 (1H, s), 12.60-13.70 (1H, br).

Workup

  1. waitThe reaction mixture was left
  2. temperatureto be cooled
  3. concentrationconcentrated under reduced pressure
  4. additionthe resulting mixture was acidified by the addition of 1 mol/L hydrochloric acid (7.8 mL)
  5. stirringAfter stirring at room temperature for 1 hour
  6. filtrationthe precipitate was collected by filtration
  7. washwashed with water
  8. customdried under reduced pressure
  9. additionThe suspension of the solid in ethanol
  10. temperaturewas heated
  11. temperatureunder reflux
  12. customto give a solution
  13. waitThe solution was left
  14. temperatureto be cooled
  15. filtrationThe precipitate was collected by filtration
  16. customdried under reduced pressure

Sources & evidence

ORD record
ord-dbf61ac7be7c416b944fc25707c7335c
Source dataset
uspto-grants-2014_08
Patent number
US08815903B2

Reaction notes

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