A practical synthesis of 2-substituted 5-bromoindoles

Article abstract of DOI:10.3987/COM-18-13893

– This paper describes a non-cryogenic synthetic procedure for a variety of 2-substituted 5-bromoindoles. The direct magnesiation of 5-bromo-1-(4-toluenesulfonyl)indole with a mixture of i-PrMgCl/LiCl and diisopropylamine allows for the preparation of var

Full text of DOI:10.3987/COM-18-13893

Supplementary Information
A PRACTICAL SYNTHESIS OF 2-SUBSTITUTED-5-BROMO-INDOLES
Yang He,a Lianlian Fan,b Haoting Zhu,a Xiaolin Li,a Pu Zhou,a and Yu Luoa,*
a Shanghai Engineering Research Center of Molecular Therapeutics and New Drug
Development, School of Chemistry and Molecular Engineering, East China Normal
University, Shanghai 200241, China. E-mail: yluo@chem.ecnu.edu.cn
b Department of Pharmacy, China-Japan Union Hospital of Jilin University, Changchun,
China
5-Bromo-1-tosyl-1H-indole (3b). To a suspension of sodium hydride (60% in mineral oil, 0.30 g,
7.7 mmol) in DMF (5.0 mL), a solution of compound 2 (1.00 g, 5.1 mmol) in DMF (5.0 mL) was
added and the mixture was stirred at 0 ºC for 1 h. To the mixture was added a solution of
4-methylbenzenesulfonyl chloride (1.17 g, 6.1 mmol) in DMF (5.0 mL) and the mixture was
stirred at room temperature for 4 h. The mixture was poured into water (100 mL) and the resulting
precipitate was collected by suction filtration, washed with water (200 mL) and dried. The crude
material was purified by flash column chromatography eluting with 5-10% EtOAc/petroleum
ether to provide 3b as a white solid (1.63 g, 91%). mp 132-134 ºC (lit.1 134 ºC); 1H NMR (CDCl3,
400 MHz), δ 7.77 (d, J = 8.7 Hz, 1H), 7.65 (d, J = 7.7 Hz, 2H), 7.44-7.60 (m, 2H), 7.31 (d, J = 8.6
Hz, 1H), 7.13 (d, J = 7.7 Hz, 2H), 6.50 (s, 1H), 2.25 (s, 3H); 13C NMR (CDCl3, 100 MHz), δ
145.3, 135.0, 133.5, 132.5, 130.0, 127.6, 127.5, 126.8, 124.1, 116.8, 115.0, 108.3, 21.6.
REFERENCES
1. D. Schäfer, J. Ermert, J. C. Meleán, and B. Neumaier, Eur. J. Org. Chem., 2016, 27, 4621.

1H NMR of compound 3b
13C NMR of compound 3b

1H NMR of compound 1
13C NMR of compound 1

1H NMR of compound 4b
13C NMR of compound 4b

IR of compound 4b
1H NMR of compound 5a

13C NMR of compound 5a
IR of compound 5a

1H NMR of compound 5b
13C NMR of compound 5b

IR of compound 5b
1H NMR of compound 5c

13C NMR of compound 5c
IR of compound 5c

1H NMR of compound 5d
13C NMR of compound 5d

IR of compound 5d
1H NMR of compound 5e

13C NMR of compound 5e
IR of compound 5e

1H NMR of compound 5f
13C NMR of compound 5f

IR of compound 5f
1H NMR of compound 5g

13C NMR of compound 5g
IR of compound 5g