Chlorotrimethylsilane → 4-(5-Chloro-2,3-dihydrobenzofuran-7-yl)-1,1-difluoro-4-methylpentan-2-one

Participants

Reaction Steps

A mixture of magnesium turnings (204 mg, 8.40 mmol) and trimethylsilyl chloride (2.13 mL, 16.8 mmol) in 10 mL of DMF was treated with 4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methylpentan-2-one (1.23 g, 4.00 mmol) in 10 mL of DMF at 0° C. The resulting mixture was stirred at room temperature overnight. The mixture was filtered and concentrated in vacuo. The residue was suspended in 20 mL of THF and treated with TBAF (1 M in THF, 4.0 mL) at room temperature. After 15 minutes, the reaction was quenched with 25 mL of saturated aqueous ammonium chloride solution and diluted with 50 mL of diethyl ether. The phases were separated and the aqueous layer was extracted with three 50 mL portions of diethyl ether. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. Chromatography on SiO2 (100% hexanes to 10% diethyl ether in hexanes, gradient) afforded 550 mg of the title product (48% yield).

Provenance & Evidence