Chlorotrimethylsilane → HCID 86762582, compound

Temperature

60 °C

Zinc (4.81 g, 73.6 mmol) was suspended in THF (6 mL), treated with 1,2-dibromoethane (0.313 mL, 3.63 mmol) and the resulting mixture was heated at 60° C. under argon for 30 minutes. The reaction mixture was allowed to cool to room temperature, treated with trimethylchlorosilane (0.120 mL, 0.938 mmol) and the resulting mixture was stirred at room temperature for 30 minutes. A solution of iodomethyl benzoate (Intermediate 23, 3.15 g, 12.02 mmol) in THF (6 mL) was added and the resulting mixture was stirred at room temperature for 1 hour. This reaction mixture was added to a solution of 4,6-dichloropyrimidine (1.075 g, 7.21 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.695 g, 0.601 mmol) in THF (11 mL) and the resulting mixture was stirred at room temperature under argon for 18 hours. The reaction mixture was filtered through celite, diluted with saturated ammonium chloride solution and extracted with ethyl acetate (×2). The ethyl acetate layers were combined, dried under magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography (Biotage SP4) eluting with a gradient of 0-20% ethyl acetate and isohexane. Product containing fractions were combined and evaporated under reduced pressure to give the title compound as a yellow solid (394 mg);

1. temperatureto cool to room temperature
2. stirringthe resulting mixture was stirred at room temperature for 1 hour
3. stirringthe resulting mixture was stirred at room temperature under argon for 18 hours
4. filtrationThe reaction mixture was filtered through celite
5. additiondiluted with saturated ammonium chloride solution
6. extractionextracted with ethyl acetate (×2)
7. customdried under magnesium sulfate
8. customevaporated under reduced pressure
9. customThe residue was purified by column chromatography (Biotage SP4)
10. washeluting with a gradient of 0-20% ethyl acetate and isohexane
11. additionProduct containing fractions
12. customevaporated under reduced pressure

ORD record

ord-6fe6fad2eb4f48868146112248a078a8

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796283B2