tert-Butyl 5-bromoindole-1-carboxylate

Uses

N-Boc-5-bromoindole is formed as an intermediate for the synthesis of di-Boc-protected 5-aminoindole via a Buchwald-Hartwig amination with tBu-carbamate followed by regioselective bromination[1].

General Description

N-Boc-5-bromoindole can undergo Sonogashira coupling reaction with N,N-diisopropylprop-2-ynylamine to afford the corresponding propargylic diisopropylamine. N-Boc-5-bromoindole is formed as an intermediate during the synthesis of 2-(5-substituted-1H-indol-3-yl)-N-hydroxyacetamide derivatives.

Synthesis

5-Bromoindole (5.0 g, 25.5 mmol), di-tert-butyl dicarbonate (7.6 mL, 33.1 mmol) and 4-dimethylaminopyridine (0.15 g, 1.23 mmol) were dissolved in acetonitrile (50 mL) and the reaction was stirred for 3 h at room temperature. After completion of the reaction, aqueous citric acid was added to the reaction mixture and extracted with ethyl acetate. The organic phase was washed with aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give N-tert-butoxycarbonyl-5-bromoindole (7.8 g, 100% yield) as a light yellow oil.

References

[1] Christoffer Bengtsson, et al. Rapid Construction of a Chloromethyl-Substituted Duocarmycin-like Prodrug. Molecules. 2023 Jun 16;28(12):4818. DOI:10.3390/molecules28124818