Methane → HCID 154494353, compound

Temperature

80 °C

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.

1. temperaturemaintaining the internal temperature below 35° C
2. temperaturecooled to room temperature
3. temperatureThe mixture was warmed to room temperature
4. stirringto stir for 30 min after which
5. stirringstirring
6. customto split
7. customThe phases were separated
8. filtrationThe upper organic phase was filtered through a pre-packed charcoal column (200 g) with aid of additional 2-methyltetrahydrofuran (1.0 L)
9. concentrationThe solution was concentrated
10. additionThe mixture was diluted with fresh 2-methyltetrahydrofuran (4.0 L)
11. concentrationconcentrated under vacuum until 4.0 L of distillate
12. customhad been collected
13. customresulting in the precipitation of a crystalline solid
14. stirringThe slurry was stirred for 1 h
15. filtrationfiltered
16. washThe wet cake was washed with 2-methyltetrahydrofuran (800 mL)
17. customdried under vacuum with a nitrogen sweep

ORD record

ord-c714ffa7024d438a8d5401be1c198144

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09416109B2