Diisopropylamine → 4-Chloro-5-(trimethylsilyl)thiophen-2-ylboronic acid

Temperature

0 °C

To a solution of diisopropyl amine (1.8 ml, 13 mmol) at 0° C. in 50 mL anhdrous THF under nitrogen was added butyllithium, 2.5 M in hexanes (4.6 ml, 12 mmol). The solution was allowed to stir 5 min and then was cooled to −78° C. (3-Chlorothiophen-2-yl)trimethylsilane (2.0 g, 10 mmol) in 5 mL THF at RT was added slowly via cannula, dropwise, over about 10 min. The resulting solution was allowed to stir for 30 min, at which point trimethyl borate (2.4 ml, 21 mmol) was added dropwise. The solution was allowed to stir for 1 h, and was then warmed to 0° C. and quenched by the addition of 25 mL of 2NHCl, and warmed to ambient temperature with stirring. The mixture was extracted three times with DCM, and the combined organics were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give a semisolid. Purification by silica gel chromatography, (0-40% EtOAc/hexanes) provided 4-chloro-5-(trimethylsilyl)thiophen-2-ylboronic acid as an off-white solid.

1. additionwas added slowly via cannula
2. waitdropwise, over about 10 min
3. additionwas added dropwise
4. stirringto stir for 1 h
5. customquenched by the addition of 25 mL of 2NHCl, and
6. temperaturewarmed to ambient temperature
7. stirringwith stirring
8. extractionThe mixture was extracted three times with DCM
9. dry with materialthe combined organics were dried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customto give a semisolid
13. customPurification by silica gel chromatography, (0-40% EtOAc/hexanes)

ORD record

ord-2d3e62ff463543fa929b2dc1f8418cca

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08686155B2