Phosphoric Acid → (5-methyl-1H-indol-4-yl)boronic acid

HRID 606295Notes

Reaction equation

HRID 606295 reaction equation
Br[C:2]1[C:10]([CH3:11])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[H-].[K+].C([Li])(C)(C)C.C([O:23][B:24](OCCCC)[O:25]CCCC)CCC.P(=O)(O)(O)O>CCOCC>[CH3:11][C:10]1[CH:9]=[CH:8][C:7]2[NH:6][CH:5]=[CH:4][C:3]=2[C:2]=1[B:24]([OH:25])[OH:23]

Participants

7

Reactant 5

HCID 1004Phosphoric AcidHCID 12712Tributyl borateHCID 82127Potassium hydrideHCID 104886354-bromo-5-methyl-1H-indoleHCID 178418306HCID 178418306, compound

Product 1

HCID 59678155(5-methyl-1H-indol-4-yl)boronic acidYield 34.6%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent4×

Conditions

Temperature
-78 °C

Procedure

A solution of 4-bromo-5-methylindole (800 mg, 3.8 mmol) in anhydrous ether (8 mL) is added with stirring to a suspension of potassium hydride (560 mg, 4.2 mmol, 30% dispersion in mineral oil) in anhydrous ether at 0° C. under argon. The resulting mixture is cooled to −78° C. and tert-butyllithium (4.9 mL of 1.7 M in pentane, 8.4 mmol) is slowly added. The resulting cream-colored mixture is stirred at −78° C. for 1 hour. Tributylborate (3.1 mL, 11.4 mmol) is slowly added and the reaction mixture is stirred for 1 hour at −78° C. before being allowed to slowly warm to room temperature. More anhydrous ether is added to facilitate stirring. After stirring for 24 hours, the resulting sticky mixture is diluted with ether and transferred in portions with stirring to a precooled solution of 1 M phosphoric acid (50 mL). After stirring for 30 minutes, the acidic mixture is extracted with diethyl ether (75 mL×3) and the combined extracts are extracted with 1 N sodium hydroxide (20 mL×4). The combined base extracts are cooled with an ice bath, acidified with 1 M phosphoric acid and extracted with ethyl acetate (20 mL×3). The combined extracts are washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered and concentrated to obtain a beige residue. The residue is triturated with hexane to obtain the desired 5-methylindole-4-boronic acid as a beige gum (230 mg).

Workup

  1. stirringthe reaction mixture is stirred for 1 hour at −78° C.
  2. temperatureto slowly warm to room temperature
  3. stirringto facilitate stirring
  4. stirringAfter stirring for 24 hours
  5. stirringAfter stirring for 30 minutes
  6. extractionthe acidic mixture is extracted with diethyl ether (75 mL×3)
  7. extractionthe combined extracts are extracted with 1 N sodium hydroxide (20 mL×4)
  8. temperatureThe combined base extracts are cooled with an ice bath
  9. extractionextracted with ethyl acetate (20 mL×3)
  10. washThe combined extracts are washed with brine (20 mL)
  11. dry with materialdried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customto obtain a beige residue
  15. customThe residue is triturated with hexane

Sources & evidence

ORD record
ord-10b3eec4ef0a4deba01a71182dc0c762
Source dataset
uspto-grants-2011_03
Patent number
US07915288B2

Reaction notes

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