Hydrochloric Acid → 1,5-dimethyl-1H-indole-2-boronic acid

HRID 226037Notes

Reaction equation

HRID 226037 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([CH3:11])=[CH:8][CH:9]=2)[CH:4]=[CH:3]1.C([Li])CCC.[B:17](OC)([O:20]C)[O:18]C.Cl.[OH-].[Na+]>C1COCC1>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([CH3:11])=[CH:8][CH:9]=2)[CH:4]=[C:3]1[B:17]([OH:20])[OH:18]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8470Trimethyl borateHCID 14798Sodium HydroxideHCID 1413791,5-DimethylindoleHCID 178418339Butyllithium

Product 1

HCID 585062151,5-dimethyl-1H-indole-2-boronic acidYield 12%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 0° C. solution of 1,5-dimethyl-1H-indole (1.10 g, 7.58 mmol) and THF (15 mL) is added 1.6M n-Bu—Li (5.7 mL, 9.09 mmol) the solution is warmed to ambient temperature and stirred for 1 h. The solution is cooled to 0° C. and B(OMe)3 (1.01 mL, 9.09 mmol) is added. The solution is warmed to ambient temperature and stirred overnight. 1M HCl (20 mL) is added and the pH adjusted to 7 with 1M NaOH. The aqueous phase is extracted with EtOAc (2×30 mL). The combined organic layers are washed with brine, dried over MgSO4, filtered and concentrated. The solids are triturated with hexane, and recrystallized from toluene/hexane to furnish the title compound (0.17 g, 0.90 mmol, 12%). 1H NMR (CDCl3), δ 2.38 (s, 3H), 4.08 (s, 3H), 6.91 (s, 1H), 6.99 (d, J=8.9 Hz, 1H), 7.29-7.38 (m, 2H) ppm. LC/MS (m/z): calcd. for C10H12BNO2 (M+H)+: 190.1. found: 146.1.

Workup

  1. temperatureThe solution is cooled to 0° C.
  2. temperatureThe solution is warmed to ambient temperature
  3. stirringstirred overnight
  4. extractionThe aqueous phase is extracted with EtOAc (2×30 mL)
  5. washThe combined organic layers are washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe solids are triturated with hexane
  10. customrecrystallized from toluene/hexane

Sources & evidence

ORD record
ord-749c9fbfde7346deb6aefd846c734317
Source dataset
uspto-grants-2009_07
Patent number
US07557103B2

Reaction notes

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