Hexane → 6-fluoro-1-[tris(propan-2-yl)silyl]-1H-indole

HRID 634296Notes

Reaction equation

HRID 634296 reaction equation
C([Li])CCC.CCCCCC.[F:12][C:13]1[CH:21]=[C:20]2[C:16]([CH:17]=[CH:18][NH:19]2)=[CH:15][CH:14]=1.[CH:22]([Si:25](Cl)([CH:29]([CH3:31])[CH3:30])[CH:26]([CH3:28])[CH3:27])([CH3:24])[CH3:23]>C1COCC1>[F:12][C:13]1[CH:21]=[C:20]2[C:16]([CH:17]=[CH:18][N:19]2[Si:25]([CH:29]([CH3:31])[CH3:30])([CH:26]([CH3:28])[CH3:27])[CH:22]([CH3:24])[CH3:23])=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 8058HexaneHCID 139400Triisopropylsilyl chlorideHCID 3512786-FluoroindoleHCID 178418339Butyllithium

Product 1

HCID 117162536-fluoro-1-[tris(propan-2-yl)silyl]-1H-indoleYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Prepared according to: Schlosser, M.; Ginanneschi, A.; Leroux, F. Eur. J. Org. Chem. 2006, 2956-2969. In a 500 mL round bottomed flask, THF (75 mL) was cooled to −78° C. and treated with a butyllithium solution, 1.6 M in hexane (23.12 mL, 37.0 mmol), 6-fluoroindole (5.00 g, 37.0 mmol) and triisopropylsilyl chloride (7.92 mL, 37.0 mmol). The solution was then removed from the cooling bath and warmed to RT and stirred for 1 h. The reaction mixture was concentrated on the rotovap and the crude residue was purified on the ISCO Combiflash Companion (40 g Redisep column, using a gradient of 0-10% EtOAc in hexanes) affording 6-fluoro-1-(triisopropylsilyl)-1H-indole (9.78 g, 33.6 mmol, 91% yield) as a clear, viscous colorless oil. MS (ESI, pos. ion) m/z 292.1 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm 7.51 (1H, dd, J=8.4, 5.9 Hz), 7.13-7.23 (2H, m), 6.83-6.92 (1H, m), 6.59 (1H, d, J=2.3 Hz), 1.68 (3H, quin, J=7.5 Hz), 1.14 (18H, d, J=7.6 Hz).

Workup

  1. customPrepared
  2. customThe solution was then removed from the cooling bath
  3. concentrationThe reaction mixture was concentrated on the rotovap
  4. customthe crude residue was purified on the ISCO Combiflash Companion (40 g Redisep column

Sources & evidence

ORD record
ord-7ff3578450d5479ebdb58210f5360f08
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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