Cyclohexanecarbonyl chloride → Cyclohexyl-[5-(4-methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophen-2-yl]-methanone

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Reaction Steps

A solution of 4-Methyl-3-thiophen-2-yl-5-trifluoromethyl-isoxazole (Preparative Example 21, 468 mg, 2.0 mmol) in dichloromethane (20 mL) was treated with FeCl3 (324 mg, 2.0 mmol) followed by cyclohexylcarbonyl chloride (268 μL, 05. mmol). The reaction was heated at reflux for 20 hours followed by evaporation and partitioning between EtOAc (25 mL) and an aqueous 1N hydrochloric acid solution (25 mL). The organic portion was then washed with a second portion of 1N hydrochloric acid solution and brine, dried over MgSO4, filtered, and concentrated in vacuo to afford crude product. The crude product was then chromatographed on silica gel with EtOAc/hexanes (3%) as eluant to afford product as a colorless solid (240 mg, 35%). 1H NMR (CDCl3) 1.24-1.76 (m, 6 H), 1.84-1.94 (m, 4 H), 2.37 (d, J=1.3, 3 H), 3.05-3.15 (m, 1 H), 7.54 (d, J=4.0, 1 H), 7.74 (d, J=4.0, 1 H). 13C NMR 7.9, 25.9, 26.0, 29.7, 47.8, 114.8, 118.7 (q, J=271), 129.1, 131.6, 135.5, 146.0, 155.4 (q, J=41), 158.0, 196.8. 19F NMR −63.1. LC/MS 7.92 min, [M+1]+ 344.

Provenance & Evidence