Sulfoxonium, trimethyl-, iodide (1:1) → Tert-butyl 2-(4-bromophenyl)cyclopropanecarboxylate

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Reaction Steps

In a round-bottom flask, mixed trimethylsulfoxonium iodide (6.6 g, 30 mmol) in dimethyl sulfoxide (28 mL, KF=266 ppm H2O) and dimethylacetamide (12 mL, KF=249 ppm H2O). Added sodium tert-butoxide (2.7 g, 28 mmol) in one portion. Stirred the suspension for NLT 0.5 H at room temperature. Separately, mixed (E)-tert-butyl 3-(4-bromophenyl)acrylate 1 (5.66 g, 20 mmol) in dimethyl sulfoxide (20 mL) and heated to 50° C. Then, transferred the sulfur ylide mixture (slight suspension) by cannula (<10 min addition). The flask/cannula were rinsed into the reaction mixture with dimethyl sulfoxide (2-4 mL). Stirred the resulting yellow solution at 50° C., monitoring by HPLC for reaction completion (<1% pA of 1 after 0.5 h). Cooled the reaction mixture to <10° C. before quenching (exothermic) by slow addition with water (120 mL, product precipitates). The resulting product slurry was stirred at room temperature (1-2 h) and then filtered. The flask and wetcake were washed with water (˜70 mL total). The wetcake was dried under vacuum at 45° C. Isolated 4.44 g of an off-white solid (98% pA, 96 wt %) in 71% wt-adjusted yield. A sample of the isolated product was further purified by crystallization from methanol/water (1:1, 20 mL/g). 1H NMR (400 MHz, CDCl3) δ 1.16-1.21 (m, 1H), 1.47 (s, 9H), 1.50-1.55 (m, 1H), 1.77-1.81 (m, 1H), 2.37-2.41 (m, 1H), 6.95 (d, 2H, J=8.37), 7.37 (d, 2H, J=8.51). 13C NMR (100 MHz, CDCl3) δ 17.3, 25.4, 25.5, 28.4, 80.7, 119.7, 127.5, 131.1, 139.2, 171.7 with 4 peaks overlapping.

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