Water → HCID 46934604, compound

Temperature

80 °C

Degassed 1,4-dioxane (600 mL) was added to palladium(II) acetate (4.80 g, 21.37 mmol) under N2. n-Butyl vinyl ether (275 mL, 2.137 mol), 2,4,5-trichloropyrimidine (200 g, 1.069 mol) and DIPEA (194 mL, 1.122 mol) were then added. The mixture was heated to 80° C. for 22.5 h and then cooled to 30° C. Palladium acetate (2.40 g, 10.68 mmol), n-butyl vinyl ether (138 mL, 1.068 mol) and DIPEA (97 mL, 561 mmol) were then added. The mixture was then heated to 80° C. for 4 h and then allowed to cool to r.t. overnight. The mixture was then added to water (2 L), and then sat. brine (2 L) was added. The phases were separated and the aqueous solution was extracted with methyl-tert-butylether (2×1 L). The combined organic solutions were washed with water resulting in an emulsion which would not separate. Everything was filtered and the two phases were then separated. The organic solution was dried (MgSO4) and concentrated to give a brown oil (240 g). This material is was split into two batches and each purified by FCC, eluting with 0-100% heptane in CH2Cl2 to give the title compound (130 g, 49%) as a yellow oil; 1H NMR: 0.89-0.97 (3H, t), 1.33-1.45 (2H, m), 1.62-1.72 (2H, m), 4.13 (2H, t), 6.08 (1H, d), 8.06 (1H, d), 8.64 (1H, s); m/z: ES+ MH+ 247.41.

1. customDegassed 1,4-dioxane (600 mL)
2. temperaturecooled to 30° C
3. temperatureThe mixture was then heated to 80° C. for 4 h
4. temperatureto cool to r.t. overnight
5. customThe phases were separated
6. extractionthe aqueous solution was extracted with methyl-tert-butylether (2×1 L)
7. washThe combined organic solutions were washed with water resulting in an emulsion which would not
8. customseparate
9. filtrationEverything was filtered
10. customthe two phases were then separated
11. dry with materialThe organic solution was dried (MgSO4)
12. concentrationconcentrated

ORD record

ord-2c4a9fbc2ce4451d98ff51bd662d2fae

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08946235B2