Sodium Hydroxide → 5-(1H-indol-4-yl)-nicotinic acid

HRID 1826723Notes

Reaction equation

HRID 1826723 reaction equation
[OH-].[Na+].CC1(C)C(C)(C)OB([C:11]2[CH:19]=[CH:18][CH:17]=[C:16]3[C:12]=2[CH:13]=[CH:14][NH:15]3)O1.Br[C:22]1[CH:23]=[N:24][CH:25]=[C:26]([CH:30]=1)[C:27]([OH:29])=[O:28]>[Pd].C1COCC1>[NH:15]1[C:16]2[C:12](=[C:11]([C:22]3[CH:23]=[N:24][CH:25]=[C:26]([CH:30]=3)[C:27]([OH:29])=[O:28])[CH:19]=[CH:18][CH:17]=2)[CH:13]=[CH:14]1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 887075-Bromonicotinic acidHCID 113224711H-Indole-4-boronic acid, pinacol ester

Product 1

HCID 221354775-(1H-indol-4-yl)-nicotinic acidYield 48.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Palladium catalyst Pd(PPh3)4 (693 mg, 0.6 mmol) and freshly prepared aqueous sodium hydroxide (3.2 g in 29 mL of water) were added to a mixture of 4-(4,4,5,5-tetramethyl[1,3,2]-dioxaborolan-2-yl)-1H-indole (4.9 g, 20.2 mmol) and 5-bromonicotinic acid (4.04 g, 20 mmol) in THF (70 mL). The system was degassed and then purged three times with nitrogen. The mixture was refluxed under nitrogen for 6 hours. It was then cooled to room temperature and ethyl acetate (400 mL) added. The organic layer was separated and washed twice with 2N NaOH solution. The aqueous layer and hydroxide washes were combined, washed with dichloromethane and then acidified with 6N HCl. The resulting precipitate was collected by vacuum filtration, washed with water and dried to give 2.3 g (48%) 5-(1H-indol-4-yl)-nicotinic acid.

Workup

  1. customThe system was degassed
  2. custompurged three times with nitrogen
  3. temperatureThe mixture was refluxed under nitrogen for 6 hours
  4. additionethyl acetate (400 mL) added
  5. customThe organic layer was separated
  6. washwashed twice with 2N NaOH solution
  7. washwashed with dichloromethane
  8. filtrationThe resulting precipitate was collected by vacuum filtration
  9. washwashed with water
  10. customdried

Sources & evidence

ORD record
ord-2d2c8d396fea424c9f82a9c4ded759d0
Source dataset
uspto-grants-2006_05
Patent number
US07053086B2

Reaction notes

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