Triethylamine → (2-Fluoropyridin-4-yl)methyl methanesulfonate

Participants

Reaction Steps

To a stirred solution of (2-Fluoro-pyridin-4-yl)-methanol (37) (381 mg, 3 mmol) in chloroform (30 ml) at 0° C. (ice bath), was added triethylamine (630 μl, 4.5 mmol) followed by methanesulfonyl chloride (270 μl, 3.6 mmol). After stirring for 1.5 hr., the mixture was diluted with dichloromethane, washed with aqueous saturated sodium bicarbonate solution, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was further dried in high vacuo to provide Methanesulfonic acid 2-fluoro-pyridin-4-ylmethyl ester (38). A flask was charged with Methanesulfonic acid 2-fluoro-pyridin-4-ylmethyl ester (38) from above, 3-(5-Isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-5-methyl-benzonitrile (32) (891 mg, 3 mmol), anhydrous powdered potassium carbonate (408 mg, 3 mmol), and lithium iodide (402 mg, 3 mmol). Anhydrous DMF (15 ml) was then added into the mixture and stirred for 5.5 hr at room temperature. The mixture was evaporated in vacuo. The residue was dissolved in methanol-dichloromethane (1:9), filtered through celite pad, and evaporated in vacuo to give a pale yellow foam. The crude product was purified by silica gel column chromatography (eluent, methanol:chloroform (2:98)) to afford 366 mg (30%) of Example H as a pale yellow foam, which was recrystallized from chloroform-ether to give a white solid; 1H NMR (200 MHz, CDCl3) δ: 1.12 (3H, d, J=6.8 Hz), 1.23 (3H, d, J=6.8 Hz), 2.25 (1H, m), 2.42 (3H, s), 4.66 (1H, d, J=16.7 Hz), 4.93 (1H, d, J=16.7 Hz), 6.61 (1H, s), 6.90 (1H, d, J=5.3 Hz), 7.71 (2H, s), 7.91 (1H, s), 8.04 (1H, d, J=5.3 Hz), 9.44 (1H, s); m/z (EI): 406 (M+); HRMS (EI) Calcd. 406.144104, Found 406.144119.

Provenance & Evidence