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

HRID 2378556Notes

Reaction equation

HRID 2378556 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[CH3:11].C([Li])(C)(C)C.[B:17](OC(C)C)([O:22]C(C)C)[O:18]C(C)C.P(=O)(O)(O)O>C1COCC1.CCCCC>[CH3:11][N:6]1[C:7]2[CH:8]=[CH:9][CH:10]=[C:2]([B:17]([OH:22])[OH:18])[C:3]=2[CH:4]=[CH:5]1

Participants

7

Reactant 4

HCID 1004Phosphoric AcidHCID 21531Triisopropyl borateHCID 225589374-Bromo-1-methyl-1H-indoleHCID 178418306HCID 178418306, compound

Product 1

HCID 22558942(1-Methyl-1H-indol-4-yl)boronic acid

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of Intermediate 67 (4.90 g) in anhydrous THF (30 ml) was cooled to −78° C. under argon gas atmosphere, then added dropwise with a 1.62 M solution of t-butyllithium in pentane (28.8 ml) over 30 minutes, and stirred for 30 minutes. This reaction mixture was added dropwise with (iPrO)3B (10.77 ml) over 10 minutes, stirred for 1 hour, then warmed to room temperature, and further stirred for 2.5 hours. The reaction mixture was poured into 1.2 N aqueous phosphoric acid (250 ml) containing ice, and extracted with diethyl ether (200 ml×3). The organic layer was extracted with 0.4 N aqueous sodium hydroxide (150 ml×3), and the aqueous layer was made acidic with 5 N hydrochloric acid under ice cooling, and extracted with diethyl ether (200 ml×3) again. The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure. The residue was washed with hexane to obtain the title compound (Intermediate 68, 3.17 g).

Workup

  1. stirringstirred for 1 hour
  2. stirringfurther stirred for 2.5 hours
  3. additioncontaining ice
  4. extractionextracted with diethyl ether (200 ml×3)
  5. extractionThe organic layer was extracted with 0.4 N aqueous sodium hydroxide (150 ml×3)
  6. extractionextracted with diethyl ether (200 ml×3) again
  7. washThe organic layer was washed with saturated brine
  8. customdried
  9. customthe solvent was evaporated under reduced pressure
  10. washThe residue was washed with hexane

Sources & evidence

ORD record
ord-8973a0a78d374040a79f532c24393313
Source dataset
uspto-grants-2008_12
Patent number
US07470807B2

Reaction notes

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