Hydrochloric Acid → {1-[tert-Butyl(dimethyl)silyl]-5-fluoro-1H-indol-4-yl}boronic acid

Temperature

-78 °C

To a solution of 1-(tert-butyl-dimethyl-silanyl)-5-fluoro-1H-indole (30.0 g, 0.12 mol) in anhydrous THF (1000 mL) were added N,N,N′,N′-tetramethylethylenediamine (36.6 mL, 0.241 mol) and a solution of s-butyl lithium (1.4 M in cyclohexane, 172 mL, 0.241 mmol) at −78° C. The resulting mixture was stirred at −78° C. for 2 h, then triisopropyl borate (37.5 mL, 162.7 mmol) was added dropwise. The resulting solution was stirred at −78° C. for 40 min, then allowed to warm to −20° C. An aqueous solution of HCl (2.4 M, 250 mL) was added and the resulting mixture was poured into H2O. The layers were separated and the aqueous layer extracted with EtOAc. The combined organic layers were dried (MgSO4) and concentrated in vacuo. The resultant yellow solid was then crystallised from DCM and cyclohexane to give the title compound as a white solid (25.0 g, 71%).

1. customat −78° C
2. stirringThe resulting solution was stirred at −78° C. for 40 min
3. temperatureto warm to −20° C
4. customThe layers were separated
5. extractionthe aqueous layer extracted with EtOAc
6. dry with materialThe combined organic layers were dried (MgSO4)
7. concentrationconcentrated in vacuo
8. customThe resultant yellow solid was then crystallised from DCM and cyclohexane

ORD record

ord-2a096c4ffe9c431890144a74705121c7

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07893060B2