Hydrochloric Acid → Dimethyl-(3-(trifluoromethyl)-phenyl)-malonate

Participants

Reaction Steps

Dioxane (100 mL) was purged with nitrogen gas for 10 minutes. Phenanthrolene (1.0 g) and copper (I) iodide (1.0 g) were added to the dioxane, the suspension was allowed to stir under a nitrogen atmosphere for 5 minutes, and then cesium carbonate (18.72 g, 57.45 mmol), dimethyl malonate (5.46 g, 50.6 mmol), and 1-iodo-3-(trifluoromethyl)benzene (12.5 g, 46.0 mmol) were added. The reaction mixture was heated to reflux for 18 hours and then cooled to room temperature. Aqueous 1N HCl was added to the reaction mixture, the layers were separated, and the aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers were dried over magnesium sulfate and filtered. Celite® diatomaceous filter aid (5 g) was added to the filtrate, and the resulting suspension was concentrated under reduced pressure at 50° C. to yield a solid consisting of the crude product adsorbed onto Celite®. This solid was purified by silica gel chromatography eluting with a gradient of 100% hexanes to 25% ethyl acetate in hexanes to yield 7.36 g (58.0%) of the title product. 1H NMR (CDCl3) δ 7.59-7.65 (m, 3H), 7.49 (t, 1H), 4.70 (s, 1H), 3.76 (s, 6H).

Provenance & Evidence