Sodium hydride → 2-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-indole

HRID 1405299Notes

Reaction equation

HRID 1405299 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([CH3:11])=[CH:5]2.[H-].[Na+].[Li]C(C)(C)C.[CH3:19][C:20]1([CH3:31])[C:24]([CH3:26])([CH3:25])[O:23][B:22](OC(C)C)[O:21]1>O1CCCC1>[CH3:11][C:6]1[NH:7][C:8]2[C:4]([CH:5]=1)=[CH:3][C:2]([B:22]1[O:23][C:24]([CH3:26])([CH3:25])[C:20]([CH3:31])([CH3:19])[O:21]1)=[CH:10][CH:9]=2

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 50039685-Bromo-2-methylindoleHCID 50177412-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 178418306HCID 178418306, compound

Product 1

HCID 184506482-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-indoleYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

To a solution of 5-bromo-2-methyl-1H-indole (3.0 g, 14.35 mmol) in dry tetrahydrofuran (20 ml) was added sodium hydride (900 mg, 22.5 mmol) with ice-cooling. After stifling for about 30 min, a solution of t-BuLi (27.5 ml, 1.3 M solution in hexane) was added dropwise with stifling at −78° C. under an inert atmosphere of nitrogen. The reaction mixture was warmed slowly to −40° C. over 45 min and stirred at this temperature for another 30 min. The mixture was cooled again below −78° C., followed by the addition of 4,4,5,5-tetramethyl-2-(propan-2-yloxy)-1,3,2-dioxaborolane (5.3 g, 28.49 mmol) dropwise. After warming to room temperature, the mixture was quenched with NH4Cl solution (100 ml) and extracted with ethyl acetate (3×100 ml). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the residue, which was purified by a silica gel column (2% ethyl acetate in petroleum ether) to afford 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (1.4 g, 38%). 1H NMR (300 MHz, CDCl3): δ 8.06 (s, 1H), 7.91 (s, 1H), 7.58-7.60 (t, J=7.5 Hz, 1H), 7.31 (d, J=8.1 Hz, 1H), 6.24 (s, 1H), 2.46 (s, 3H), 1.39 (s, 12H).

Workup

  1. temperaturecooling
  2. customwith stifling at −78° C. under an inert atmosphere of nitrogen
  3. temperatureThe mixture was cooled again below −78° C.
  4. temperatureAfter warming to room temperature
  5. customthe mixture was quenched with NH4Cl solution (100 ml)
  6. extractionextracted with ethyl acetate (3×100 ml)
  7. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto give the residue, which
  11. customwas purified by a silica gel column (2% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-6679036929434efc805745194eb84b87
Source dataset
uspto-grants-2014_12
Patent number
US08916561B2

Reaction notes

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