Hydrochloric Acid → DIMETHYL 2-(2-PYRIMIDYL)MALONATE

To dimethyl malonate (41.6 g) in 1,4-dioxane (900 ml) was added sodium hydride (60% dispersion in mineral oil; 18.9 g) portionwise. To the resultant gel was added 2-bromopyrimidine (50.0 g) in 1,4-dioxane (200 ml) dropwise. The mixture was stirred at room temperature for 1 h, then at reflux overnight. To the cooled solution was added water (400 ml), and 5 N hydrochloric acid until the pH was ˜1. The solution was washed with ethyl acetate (2×400 ml), the organic layers combined, washed with saturated sodium hydrogen carbonate solution (1×400 ml) and saturated sodium chloride solution (1×400 ml), dried (magnesium sulfate) and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, eluent =0 to 20% ethyl acetate in dichloromethane) to yield dimethyl 2-(pyrimidin-2-yl)malonate as a yellow/orange oil (24.1 g). 1H NMR (250 MHz, CDCl3) δ3.83 (6 H, s), 5.16 (1 H, s)7.28 (1 H, t, J=5.0 Hz), 8.87 (2 H, d, J=5.0 Hz); MS (ES+) m/e 211 [MH+].

1. temperatureat reflux overnight
2. washThe solution was washed with ethyl acetate (2×400 ml)
3. washwashed with saturated sodium hydrogen carbonate solution (1×400 ml) and saturated sodium chloride solution (1×400 ml)
4. dry with materialdried (magnesium sulfate)
5. concentrationconcentrated in vacuo
6. customThe residue was purified by flash chromatography (silica gel, eluent =0 to 20% ethyl acetate in dichloromethane)

ORD record

ord-a7786ae3544949628d0c525fb88c450d

Source dataset

uspto-grants-2001_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06255305B1