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

HRID 984711Notes

Reaction equation

HRID 984711 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])CCC.[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 178418339Butyllithium

Product 1

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

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of Intermediate 51 (4.90 g) in anhydrous THF (30 ml) was cooled to −78° C. under argon atmosphere, then added dropwise with 1.62 M solution of n-butyllithium in pentane (28.8 ml) over 30 minutes and stirred for 30 minutes. The 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) added with 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 acidified with 5 N aqueous 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 52, 3.17 g).

Workup

  1. stirringstirred for 1 hour
  2. stirringfurther stirred for 2.5 hours
  3. additionadded with 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-890bb0063f8f45168a6bb4588e6cd9e5
Source dataset
uspto-grants-2005_03
Patent number
US06867320B2

Reaction notes

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