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 (200 g, 1.03 mol) and THF (2 L) at ambient temperature. 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 vigorous 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 exothermic process 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 n-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 n-heptane (1 L) and re-concentrated. If the solids formed upon adding the n-heptane, a second filtration was 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 (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, it was found that 1-trimethylsilyl-4-iodopyrazole can be prepared by heating the iodopyrazole 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 n-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 n-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-5a51efc154bd4b9fb3b02e70fe7b2e5b

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09221845B2