Methane → HCID 154494353, compound

Participants

Reaction Conditions

Reaction Steps

2,4-Dichloro-5-methoxypyrimidine (16, 400 g, 2.23 mol, 1.0 equiv) was dissolved in 2-methyltetrahydrofuran (4.0 L). To this mixture was charged trimethylaluminum (2.0 M in heptane, 2200 mL, 2.0 equiv.), maintaining the internal temperature below 35° C. Tetrakis(triphenylphosphine)palladium(0) (25.8 g, 0.022 mol, 0.01 equiv.) was added and the mixture was heated to 80° C. The mixture was stirred for 24 h at 80° C., cooled to room temperature and added slowly to a cold (5-10° C.) aqueous sodium hydroxide solution (6 N, 4.0 L), maintaining the internal temperature of the quench solution below 15° C. (Caution: methane gas evolution). The mixture was warmed to room temperature and allowed to stir for 30 min after which stirring was halted and the phases allowed to split. The phases were separated. The upper organic phase was filtered through a pre-packed charcoal column (200 g) with aid of additional 2-methyltetrahydrofuran (1.0 L). The solution was concentrated to ⅔ volume. The mixture was diluted with fresh 2-methyltetrahydrofuran (4.0 L) and then concentrated under vacuum until 4.0 L of distillate had been collected. To the remaining solution was slowly added a solution of hydrogen chloride in isopropyl alcohol (5 M, 670 mL, 3.35 mol, 1.5 equiv.) resulting in the precipitation of a crystalline solid. The slurry was stirred for 1 h, and filtered. The wet cake was washed with 2-methyltetrahydrofuran (800 mL) and then dried under vacuum with a nitrogen sweep to afford 5-methoxy-2,6-dimethylpyrimidin-1-ium chloride (17, 279 g, 70% yield) as a pale yellow solid.

Provenance & Evidence