Potassium hydride → 2-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-indole

Temperature

-78 °C

A solution of 5-bromo-2-methyl-1H-indole (5.04 g, 24 mmol) in THF (25 mL) was added dropwise to a suspension of potassium hydride (3.2 g, 24 mmol) in THF at 0° C. After fifteen minutes at 0° C., the solution was cooled to −78° C. and a t-butyl lithium solution (1.7 M in pentane, 28.2 mL, 48 mmol) was added dropwise via syringe while maintaining the temperature below −55° C. After an additional 15 minutes, the solution was cooled to −78° C. and treated with a 2-isopropoxy-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (9.8 mL, 48 mmol) dropwise via syringe. The solution was stirred at −78° C. for 1.5 hours, allowed to warm to room temperature and quenched with saturated aqueous ammonium chloride. The solution was diluted with ethyl acetate and filtered to remove inorganic material. The filtrate was extracted with ethyl acetate. The combined organics were washed with brine, dried (MgSO4) and concentrated. The concentrate was purified by flash chromatography on silica gel using 10% ethyl acetate/hexanes to give 3.9 g (63% yield) of the desired product. MS (ESI(+)) m/e 258 (M+H)+.

1. waitAfter fifteen minutes at 0° C.
2. temperaturewhile maintaining the temperature below −55° C
3. temperaturethe solution was cooled to −78° C.
4. temperatureto warm to room temperature
5. customquenched with saturated aqueous ammonium chloride
6. additionThe solution was diluted with ethyl acetate
7. filtrationfiltered
8. customto remove inorganic material
9. extractionThe filtrate was extracted with ethyl acetate
10. washThe combined organics were washed with brine
11. dry with materialdried (MgSO4)
12. concentrationconcentrated
13. customThe concentrate was purified by flash chromatography on silica gel using 10% ethyl acetate/hexanes

ORD record

ord-2c6b03826eb748a7aec20f26756270a1

Source dataset

uspto-grants-2007_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07202363B2