2-Chloropyrimidine → 4-(4-bromo-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloropyrimidine

Participants

Reaction Conditions

Reaction Steps

n-BuLi (1.5 M in hexane, 40 mL, 60 mmol) was added dropwise to a cooled solution of 4,5-dibromo-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (23.6 g, 57.2 mmol) in anhydrous THF (250 mL) at −78° C. After 30 minutes at −78° C., a solution of 2-chloropyrimidine (7.21 g, 63.0 mmol) in anhydrous THF (2 mL) was added dropwise and the reaction was stirred at −78° C. for 1 hour. The reaction was quenched by the addition of saturated aqueous NH4Cl solution and allowed to warm to room temperature. The mixture was partitioned with EtOAc and the layers separated. The aqueous portion was extracted with EtOAc (3×) and the combine organic layers were washed with water, brine, dried (MgSO4), and concentrated. The resulting residue was dissolved in EtOAc, treated with MnO2 (5.2 g, 60 mmol), and heated to reflux for 3 hours. The reaction was allowed to cool to room temperature and filtered through Celite. The filter cake was washed thoroughly with EtOAc and the combine filtrates were concentrated. The remaining residue was purified by flash chromatography (SiO2, 0-10% EtOAc in hexanes) to give 10 g (37%) of 4-(4-bromo-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloropyrimidine: LCMS(m/z): 445.0 (MH+), tR=1.35 minutes. 1H NMR (400 MHz, CDCl3) δ 8.64 (d, J=5.3 Hz, 1H), 7.83 (d, J=5.3 Hz, 1H), 5.85 (s, 2H), 3.45 (m, 2H), 1.49 (s, 9H), 0.76 (m, 2H), −0.08 (s, 9H).

Provenance & Evidence