3-(Trifluoromethyl)benzoyl chloride → HCID 61644659, compound

Participants

Reaction Steps

To a 250-mL three-neck round-bottomed flask equipped with a thermometer, condenser, and nitrogen inlet was added Zn—Cu couple (3.41 g, 52.1 mmol). A solution of methyl 3-iodopropionate (7.27 g, 34.0 mmol) in benzene (67.7 mL) and DMA (4.5 mL) was added over 5 min and the mixture was stirred at room temperature for 1 h, then heated at 60° C. for 5 h. A mixture of Pd(PPh3)4 (1.05 g, 0.906 mmol) in benzene (22.7 mL) was added to the reaction and stirred at 60° C. for 5 min. The mixture was then removed from heat and 3-(trifluoromethyl)benzoyl chloride (3.4 mL, 23 mmol) in benzene (11.3 mL) was added immediately. After stirring for 2 h, the mixture was diluted with EtOAc, washed with 1 M HCl (3×200 mL), NaHCO3 (2×200 mL) and brine (1×200 mL), dried over Na2SO4, filtered, and evaporated. The crude material was purified by CombiFlash chromatography (silica, 0–70% ether/hexanes) to give 4-oxo-4-(3-trifluoromethylphenyl)butyric acid methyl ester (5.35 g, 91%) as an orange oil: 1H NMR (300 MHz CDCl3) δ 8.24 (s, 1H), 8.17 (d, J=7.8 Hz, 1H), 7.84 (d, J=7.8 Hz, 1H), 7.63 (t, J=7.8 Hz, 1H), 3.72 (s, 3H), 3.35 (t, J=6.5 Hz, 2H), 2.81 (t, J=6.5 Hz, 2H); 19F NMR (282 MHz, CDCl3) δ −63.3; ESI MS m/z 261 [C12H11F3O3+H]+.

Provenance & Evidence