Dimethylformamide → 5-(trifluoromethyl)-1H-indole-7-carbaldehyde

Temperature

0 °C

To a −78° C. solution of 7-bromo-5-(trifluoromethyl)-1H-indole (8.77 g, 33.2 mmol) in tetrahydrofuran (200 mL), n-BuLi (1.6 M in hexanes, 72.7 mL, 116 mmol) was added slowly. The reaction was warmed to 0° C. and stirred for 15 min. The reaction was recooled to −78° C., treated with dimethylformamide (12.9 mL, 166 mmol), warmed to ambient temperature, and stirred for 30 min. The reaction was quenched by slow addition of 1N hydrochloric acid (50 mL) and was then extracted with ethyl acetate (2×40 mL). The organic layers were dried (magnesium sulfate) and evaporated. The residue was purified by chromatography on silica gel with 15% ethyl acetate/hexanes. The product 5-(trifluoromethyl)-1H-indole-7-carbaldehyde (5.95 g, 27.9 mmol, 84% yield) was obtained as an orange solid. 1H-NMR (CDCl3, 400 MHz) δ 10.28 (bs, 1H), 10.16 (s, 1H), 8.20 (d, J=0.6 Hz, 1H), 7.90 (d, J=0.6 Hz), 7.45 (dd, J=3.2, 2.5 Hz, 1H), 6.72 (dd, J=3.2, 2.4 Hz, 1H).

1. customwas recooled to −78° C.
2. temperaturewarmed to ambient temperature
3. stirringstirred for 30 min
4. customThe reaction was quenched by slow addition of 1N hydrochloric acid (50 mL)
5. extractionwas then extracted with ethyl acetate (2×40 mL)
6. dry with materialThe organic layers were dried (magnesium sulfate)
7. customevaporated
8. customThe residue was purified by chromatography on silica gel with 15% ethyl acetate/hexanes

ORD record

ord-68f1f283aae845f08cfe37d31a629cc5

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08026257B2