t-Butyl bromide → 3-(1,1-Dimethylethyl)-6-nitro-5-(trifluoromethyl)-1H-indole

HRID 1805129Notes

Reaction equation

[N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][C:5]=1[C:13]([F:16])([F:15])[F:14])([O-:3])=[O:2].[C:17](Br)([CH3:20])([CH3:19])[CH3:18].CCN(C(C)C)C(C)C>CCCC[N+](CCCC)(CCCC)CCCC.[I-].[O-]S(C(F)(F)F)(=O)=O.[Zn+2].[O-]S(C(F)(F)F)(=O)=O.C1(C)C=CC=CC=1>[C:17]([C:8]1[C:7]2[C:11](=[CH:12][C:4]([N+:1]([O-:3])=[O:2])=[C:5]([C:13]([F:16])([F:14])[F:15])[CH:6]=2)[NH:10][CH:9]=1)([CH3:20])([CH3:19])[CH3:18]

Participants

Conditions

Temperature: 120 °C

Procedure

A microwave vial charged with 6-nitro-5-(trifluoromethyl)-1H-indole (100 mg, 0.43 mmol), t-butyl bromide (30 mg, 0.22 mmol), zinc triflate (95 mg, 0.26 mmol), TBAI (80 mg, 0.22 mmol), DIEA (63 mg, 0.49 mmol) and toluene (1 mL) was sealed and heated in the microwave for 10 minutes at 120° C. The reaction mixture was quenched with water, the layers separated and the aqueous layer was extracted with DCM. The combined organic layer was dried over Na2SO4, filtered and concentrated. It was then purified by silica gel column chromatography using 0 to 20% EtOAc in hexanes to obtain 3-tert-butyl-6-nitro-5-(trifluoromethyl)-1H-indole. 1H NMR (400.0 MHz, CDCl3) δ 8.25 (s, 1H), 8.10 (s, 1H), 7.33 (d, J=2.5 Hz, 1H), 7.28 (s, 1H) and 1.50 (s, 9H) ppm.

Workup

customwas sealed
customThe reaction mixture was quenched with water
customthe layers separated
extractionthe aqueous layer was extracted with DCM
dry with materialThe combined organic layer was dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customIt was then purified by silica gel column chromatography

Sources & evidence

ORD record: ord-a1369d3ccf764c4090304a6d2ee9584f
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354427B2

Reaction notes

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