Nitrogen → 6-bromo-1-(triisopropylsilyl)-1H-indole

HRID 1524380Notes

Reaction equation

HRID 1524380 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.N#N.[H-].[Na+].[CH:15]([Si:18](Cl)([CH:22]([CH3:24])[CH3:23])[CH:19]([CH3:21])[CH3:20])([CH3:17])[CH3:16]>C1COCC1>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[Si:18]([CH:22]([CH3:24])[CH3:23])([CH:19]([CH3:21])[CH3:20])[CH:15]([CH3:17])[CH3:16])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 947NitrogenHCID 24758Sodium hydrideHCID 139400Triisopropylsilyl chlorideHCID 6764936-Bromoindole

Product 1

HCID 129912436-bromo-1-(triisopropylsilyl)-1H-indoleYield 68.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
3.5 °C

Procedure

A 500 mL 3-neck round-bottom flask was charged with 6-bromo-1H-indole (5.95 g, 30.4 mmol) and THF (60 ml) to give a deep red solution. The flask was fitted with a N2 sweep, then cooled in an ice bath until an internal temperature of 2 to 5° C. was reached. At this time, sodium hydride (1.457 g, 36.4 mmol) was added portion-wise over 2 to 3 minutes such that the internal temperature was maintained below 10° C. The resulting mixture was stirred at this temperature for 20 minutes before triisopropylsilyl chloride (8.12 ml, 37.9 mmol) was added over 1 min. The cooling bath was removed, and the mixture was stirred for 15 min at room temperature. The volatiles were evaporated in vacuo, and the residue was taken up in saturated aq. sodium bicarbonate solution (150 mL). The mixture was extracted with DCM (2×250 mL), and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by chromatography on silica gel (0 to 10% EtOAc/Heptane) to give 6-bromo-1-(triisopropylsilyl)-1H-indole (7.33 g, 20.80 mmol, 68.5% yield) as a clear oil. 1H NMR (400 MHz, CDCl3) δ=8.22 (td, J=0.8, 1.5 Hz, 1 H), 7.85-7.70 (m, 2 H), 7.58 (d, J=3.1 Hz, 1 H), 6.78 (dd, J=1.0, 3.1 Hz, 1 H), 1.84-1.65 (m, 3 H), 1.17 (d, J=7.5 Hz, 18 H).

Workup

  1. customto give a deep red solution
  2. temperaturewas maintained below 10° C
  3. additionwas added over 1 min
  4. customThe cooling bath was removed
  5. customThe volatiles were evaporated in vacuo
  6. extractionThe mixture was extracted with DCM (2×250 mL)
  7. dry with materialthe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by chromatography on silica gel (0 to 10% EtOAc/Heptane)

Sources & evidence

ORD record
ord-1128dd78d6b74886b53b7ba7b2e13b6e
Source dataset
uspto-grants-2015_07
Patent number
US09079902B2

Reaction notes

Loading…