Sodium hydride → 2-methyl-6-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole

HRID 1403457Notes

Reaction equation

HRID 1403457 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([CH3:11])[NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].[Li]CCCC.[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:7]1[NH:8][C:9]2[C:5]([CH:6]=1)=[CH:4][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]=2

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 2715546-Bromo-2-methyl-1h-indoleHCID 50177412-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 178418339Butyllithium

Product 1

HCID 706646442-methyl-6-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indoleYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

To a solution of 6-bromo-2-methyl-1H-indole (2.0 g, 9.52 mmol) in dry tetrahydrofuran (100 mL) was added sodium hydride (381 mg, 9.53 mmol) with ice-cooling. After stirring for about 30 min, a solution of n-BuLi (15 mL, 2.5 M solution in hexane) was added dropwise with stirring at −78° C. under nitrogen. It was warmed slowly to −40° C. during 45 min and stirred at this temperature for another 30 min. The mixture was cooled again below −78° C. followed by dropwise addition of 4,4,5,5-tetramethyl-2-(propan-2-yloxy)-1,3,2-dioxaborolane (3.54 g, 19.03 mmol). After warming to room temperature, the mixture was quenched with NH4Cl (aq) and extracted with ethyl acetate (3×80 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 silica gel column chromatography (2% ethyl acetate in petroleum ether) to afford 2-methyl-6-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (1.2 g, 49%).

Workup

  1. temperaturecooling
  2. stirringwith stirring at −78° C. under nitrogen
  3. stirringstirred at this temperature for another 30 min
  4. temperatureThe mixture was cooled again below −78° C.
  5. temperatureAfter warming to room temperature
  6. customthe mixture was quenched with NH4Cl (aq)
  7. extractionextracted with ethyl acetate (3×80 mL)
  8. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto give the residue, which
  12. customwas purified by silica gel column chromatography (2% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-4975337309e3446695ea02baaff29d45
Source dataset
uspto-grants-2014_12
Patent number
US08912188B2

Reaction notes

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