t-Butyl bromide → 3-(tert-Butyl)-6-nitro-1h-indole

HRID 73930

Reaction equation

HRID 73930 reaction equation
[N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].CCN(C(C)C)C(C)C.[C:22](Br)([CH3:25])([CH3:24])[CH3:23]>CCCC[N+](CCCC)(CCCC)CCCC.[I-].C1(C)C=CC=CC=1.[O-]S(C(F)(F)F)(=O)=O.[Zn+2].[O-]S(C(F)(F)F)(=O)=O>[C:22]([C:8]1[C:7]2[C:11](=[CH:12][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[NH:10][CH:9]=1)([CH3:25])([CH3:24])[CH3:23]

Participants

7

Reactant 3

HCID 10485t-Butyl bromideHCID 785026-Nitro-1H-indoleHCID 81531Diisopropylethylamine

Product 1

HCID 574701983-(tert-Butyl)-6-nitro-1h-indoleYield 22.2%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 104671Zinc trifluoromethanesulfonateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of 6-nitroindole (1 g, 6.2 mmol), zinc triflate (2.06 g, 5.7 mmol) and TBAI (1.7 g, 5.16 mmol) in anhydrous toluene (11 mL) was added DIEA (1.47 g, 11.4 mmol) at room temperature under nitrogen. The reaction mixture was stirred for 10 min at 120° C., followed by addition of t-butyl bromide (0.707 g, 5.16 mmol). The resulting mixture was stirred for 45 min at 120° C. The solid was filtered off and the filtrate was concentrated to dryness and purified by column chromatography on silica gel (Pet.Ether./EtOAc 20:1) to give 3-tert-butyl-6-nitro-1H-indole as a yellow solid (0.25 g, 19%). 1H NMR (CDCl3) δ 8.32 (d, J=2.1 Hz, 1H), 8.00 (dd, J=2.1, 14.4 Hz, 1H), 7.85 (d, J=8.7 Hz, 1H), 7.25 (s, 1H), 1.46 (s, 9H).

Workup

  1. stirringThe resulting mixture was stirred for 45 min at 120° C
  2. filtrationThe solid was filtered off
  3. concentrationthe filtrate was concentrated to dryness
  4. custompurified by column chromatography on silica gel (Pet.Ether./EtOAc 20:1)

Sources & evidence

ORD record
ord-f2ad71930ecb4773ba351e9d93c9dc4e
Source dataset
uspto-grants-2014_09
Patent number
US08829204B2

Linked notes

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