Sodium hydride → Methyl (2E)-3-[6-(trifluoromethyl)pyridin-3-YL]prop-2-enoate

Participants

Reaction Steps

To a stirring solution of trimethyl phosphonoacetate (0.510 mL, 3.14 mmol) in THF (15 mL) at 0° C. was added NaH (88.0 mg, 3.3 mmol). After stirring for ca. 20 min, the slurry was allowed to warm to ambient temperature for 10 min, then cooled again to 0° C. To this was added dropwise 6-(trifluoro-methyl)nicotinaldehyde (500 mg, 2.86 mmol), which is commercially available from Oakwood Products, Inc. (1741 Old Dunbar Rd., West Columbia, S.C. 29172), in THF (5 mL) over 2 min. The bath was allowed to expire and the reaction stirred at ambient temperature for ca. 24 h. The reaction was quenched with H2O (50 mL) then diluted with EtOAc (100 mL). The phases were separated and the organics further washed with H2O (2×20 mL), brine (5 mL), dried over MgSO4, filtered and concentrated in vacuo to afford 670 mg 26A in ca. 85% purity as a white solid (86% yield). This was taken forward without further purification. m/z (ES+) M+1=232.1; HPLC tR=1.07 min. 1H NMR (500 MHz, CDCl3) δ 8.84 (dd, J=2.1, 0.6 Hz, 1H), 7.99 (dt, J=8.2, 1.2 Hz, 1H), 7.77-7.65 (m, 2H), 6.59 (d, J=16.2 Hz, 1H), 3.85 (s, 3H).

Provenance & Evidence