Chlorotrimethylsilane → HCID 21632190, compound

Temperature

0 °C

To a flask equipped with a reflux condenser, a nitrogen inlet, mechanical stirrer, and a thermowell was charged 4-iodopyrazole (14, 200 g, 1.03 mol) and THF (2 L). To this solution was added triethylamine (TEA, 158 mL, 1.13 mol, 1.1 equiv) and the resulting solution was cooled to 0° C. in an ice-brine bath. To this solution was added chlorotrimethylsilane (TMS-Cl, 137 mL, 1.08 mol, 1.05 equiv) with rapid stirring allowing the temperature to reach 18° C. (The reaction becomes very thick and difficult to stir, but becomes manageable after over time). When the exotherm had subsided, the cold bath was removed and the reaction was warmed to room temperature. The reaction was followed by GC and was found to be deemed complete after about 1 hour (Sampling of reaction must be done out of air and diluted with dry solvent to prevent TMS hydrolysis). The reaction mixture was then diluted with heptane (2 L) before being filtered under nitrogen. The solvent was removed from the filtrate under reduced pressure venting the rotovap with nitrogen. The residual oil was diluted with heptane (1 L) and re-concentrated. If the solids formed upon adding the heptane, a second filtration is necessary. The residue was then distilled under the reduced pressure (70-90° C. at about 0.5 Torr) using a Kugelohr to afford 1-trimethylsilyl-4-iodopyrazole (15, 263 g, 274.1 g theoretical, 96%) as a colorless oil. (This material must be kept under nitrogen at all times since the TMS group rapidly hydrolyzes.) Subsequently, we have found that 1-trimethylsilyl-4-iodopyrazole can be prepared by heating the iodopyrazole (14) with 2 equivalents of hexamethyldisilazane for 1 hr.

1. customTo a flask equipped with a reflux condenser, a nitrogen inlet, mechanical stirrer
2. customto reach 18° C.
3. stirringdifficult to stir
4. customthe cold bath was removed
5. temperaturethe reaction was warmed to room temperature
6. aliquot(Sampling of reaction must be done out of air and diluted with dry solvent to prevent TMS hydrolysis)
7. additionThe reaction mixture was then diluted with heptane (2 L)
8. filtrationbefore being filtered under nitrogen
9. customThe solvent was removed from the filtrate under reduced pressure
10. additionThe residual oil was diluted with heptane (1 L)
11. concentrationre-concentrated
12. customIf the solids formed
13. filtrationa second filtration
14. distillationThe residue was then distilled under the reduced pressure (70-90° C. at about 0.5 Torr)

ORD record

ord-0102bdd687794e4991a14ff5e7962d33

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09290506B2