Sodium hydride → 6-bromo-1-(triisopropylsilyl)-1H-indole

Temperature

10 °C

To a stirred solution of 6-bromo-1H-indole (2.04 g, 1.04 mmol) in THF under nitrogen at 0° C. was added sodium hydride (60%, 1.25 g 31.2 mmol), portionwise over 0.2 h. The mixture was stirred at 0-20° C. for 1 h then was cooled in an ice-MeOH bath, whereupon triisopropylsilyl trifluoromethylsulfonate (3.83 g, 12.5 mmol) was added dropwise over 3 h. The resulting mixture was stirred at 0° C. for 1 h then at 20° C. for 72 h. The mixture was quenched (caution,) with a mixture of THF (30 mL) and water (1 mL) with external ice cooling and the resulting clear solution was partitioned between water (100 mL) and DCM (3×50 mL). The combined organic extracts were dried (Na2SO4) and evaporated in vacuo to give an oil. Chromatography (SiO2; gradient elution with 0-40% Et2O in petrol) gave the title compound (3.48 g) as a colourless oil. 1H NMR (CDCl3): 7.66-7.64 (1H, m), 7.50 (1H, d), 7.25-7.21 (2H, m), 6.61 (1H, d), 1.76-1.64 (3H, m), 1.17 (18H, d).

1. additionwas added dropwise over 3 h
2. stirringThe resulting mixture was stirred at 0° C. for 1 h
3. waitat 20° C. for 72 h
4. customThe mixture was quenched (caution,)
5. additionwith a mixture of THF (30 mL) and water (1 mL) with external ice cooling
6. customthe resulting clear solution was partitioned between water (100 mL) and DCM (3×50 mL)
7. dry with materialThe combined organic extracts were dried (Na2SO4)
8. customevaporated in vacuo
9. customto give an oil
10. washChromatography (SiO2; gradient elution with 0-40% Et2O in petrol)

ORD record

ord-3942b1c56e90421a8735ab3d4a568aec

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09018214B2