Hydrochloric Acid → 1H-Indol-6-ylboronic acid

Temperature

-78 °C

A solution of 6-Bromo-1H-indole (1.5 g, 7.65 mmol) in THF (10 mL) was added dropwise to a suspension of potassium hydride (0.31 g, 7.65 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, 9.0 mL, 15.3 mmol) was added dropwise via syringe while maintaining a temperature below −55° C. After 15 minutes, the solution was cooled to −78° C. and treated with a tributyl borate (4.14 mL, 15.3 mmol). The solution was stirred at −78° C. for 2 hours and then allowed to warm to −10° C. The solution was the added 75 mL of 1 M HCl, warmed to room temperature and separated. The aqueous phase was extracted with diethyl ether (3×75 mL) and the combined organics were extracted with 1 M NaOH (4×40 mL). The aqueous layers were combined, adjusted to pH ˜2 with 6 M HCl and extracted with diethyl ether (4×50 mL). The combined organic layers were washed with brine (20 mL), dried (MgSO4), filtered and concentrated. The concentrate was purified by flash chromatography on silica gel using 3.5-5% methanol/dichloromethane to give 838 mg (68% yield) of the desired product. MS (ESI(+)) m/e 161 (M+H)+.

1. waitAfter fifteen minutes at 0° C.
2. temperaturewhile maintaining a temperature below −55° C
3. temperaturethe solution was cooled to −78° C.
4. temperatureto warm to −10° C
5. temperaturewarmed to room temperature
6. customseparated
7. extractionThe aqueous phase was extracted with diethyl ether (3×75 mL)
8. extractionthe combined organics were extracted with 1 M NaOH (4×40 mL)
9. extractionextracted with diethyl ether (4×50 mL)
10. washThe combined organic layers were washed with brine (20 mL)
11. dry with materialdried (MgSO4)
12. filtrationfiltered
13. concentrationconcentrated
14. customThe concentrate was purified by flash chromatography on silica gel using 3.5-5% methanol/dichloromethane

ORD record

ord-581c5ef60eff4db48100117d102cfcac

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08273736B2