4,4,4-三氟-1-(2-甲氧基苯基)丁烷-1,3-二酮

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Synthesis of 5-(2-methoxyphenyl)-3-(trifluoromethyl)-1,2-oxazole (C10) A mixture of 4,4,4-trifluoro-1-(2-methoxyphenyl)butane-1,3-dione (C9) (933 mg, 3.79 mmol) and hydroxylamine hydrochloride (798 mg, 11.4 mmol) in ethanol (10 mL) was refluxed under nitrogen for 3 hours, then cooled to room temperature. The reaction was concentrated in vacuo, treated with water (30 mL) and extracted with dichloromethane (3×10 mL). The combined organic layers were dried over sodium sulfate and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 0% to 20% ethyl acetate in heptanes) afforded the title compound as a yellow oil. Yield: 502 mg, 2.06 mmol, 54%. GCMS m/z 243 (M+). 1H NMR (400 MHz, CDCl3) δ 4.00 (s, 3H), 7.01 (s, 1H), 7.05 (dd, J=8.4, 0.9 Hz, 1H), 7.11 (ddd, J=7.8, 7.4, 1.1 Hz, 1H), 7.48 (ddd, J=8.4, 7.4, 1.8 Hz, 1H), 8.00 (dd, J=7.8, 1.7 Hz, 1H). was refluxed under nitrogen for 3 hours The reaction was concentrated in vacuo treated with water (30 mL) extracted with dichloromethane (3×10 mL) The combined organic layers were dried over sodium sulfate concentrated in vacuo Purification via silica gel chromatography (Gradient: 0% to 20% ethyl acetate in heptanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Synthesis of 5-(2-methoxyphenyl)-3-(trifluoromethyl)-1,2-oxazole (C10) A mixture of 4,4,4-trifluoro-1-(2-methoxyphenyl)butane-1,3-dione (C9) (933 mg, 3.79 mmol) and hydroxylamine hydrochloride (798 mg, 11.4 mmol) in ethanol (10 mL) was refluxed under nitrogen for 3 hours, then cooled to room temperature. The reaction was concentrated in vacuo, treated with water (30 mL) and extracted with dichloromethane (3×10 mL). The combined organic layers were dried over sodium sulfate and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 0% to 20% ethyl acetate in heptanes) afforded the title compound as a yellow oil. Yield: 502 mg, 2.06 mmol, 54%. GCMS m/z 243 (M+). 1H NMR (400 MHz, CDCl3) δ 4.00 (s, 3H), 7.01 (s, 1H), 7.05 (dd, J=8.4, 0.9 Hz, 1H), 7.11 (ddd, J=7.8, 7.4, 1.1 Hz, 1H), 7.48 (ddd, J=8.4, 7.4, 1.8 Hz, 1H), 8.00 (dd, J=7.8, 1.7 Hz, 1H). was refluxed under nitrogen for 3 hours The reaction was concentrated in vacuo treated with water (30 mL) extracted with dichloromethane (3×10 mL) The combined organic layers were dried over sodium sulfate concentrated in vacuo Purification via silica gel chromatography (Gradient: 0% to 20% ethyl acetate in heptanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Synthesis of 5-(2-methoxyphenyl)-3-(trifluoromethyl)-1,2-oxazole (C10) A mixture of 4,4,4-trifluoro-1-(2-methoxyphenyl)butane-1,3-dione (C9) (933 mg, 3.79 mmol) and hydroxylamine hydrochloride (798 mg, 11.4 mmol) in ethanol (10 mL) was refluxed under nitrogen for 3 hours, then cooled to room temperature. The reaction was concentrated in vacuo, treated with water (30 mL) and extracted with dichloromethane (3×10 mL). The combined organic layers were dried over sodium sulfate and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 0% to 20% ethyl acetate in heptanes) afforded the title compound as a yellow oil. Yield: 502 mg, 2.06 mmol, 54%. GCMS m/z 243 (M+). 1H NMR (400 MHz, CDCl3) δ 4.00 (s, 3H), 7.01 (s, 1H), 7.05 (dd, J=8.4, 0.9 Hz, 1H), 7.11 (ddd, J=7.8, 7.4, 1.1 Hz, 1H), 7.48 (ddd, J=8.4, 7.4, 1.8 Hz, 1H), 8.00 (dd, J=7.8, 1.7 Hz, 1H). was refluxed under nitrogen for 3 hours The reaction was concentrated in vacuo treated with water (30 mL) extracted with dichloromethane (3×10 mL) The combined organic layers were dried over sodium sulfate concentrated in vacuo Purification via silica gel chromatography (Gradient: 0% to 20% ethyl acetate in heptanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 4,4,4-trifluoro-1-(2-methoxyphenyl)butane-1,3-dione (C9) (933 mg, 3.79 mmol) and hydroxylamine hydrochloride (798 mg, 11.4 mmol) in ethanol (10 mL) was refluxed under nitrogen for 3 hours, then cooled to room temperature. The reaction was concentrated in vacuo, treated with water (30 mL) and extracted with dichloromethane (3×10 mL). The combined organic layers were dried over sodium sulfate and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 0% to 20% ethyl acetate in heptanes) afforded the title compound as a yellow oil. Yield: 502 mg, 2.06 mmol, 54%. GCMS m/z 243 (M+). 1H NMR (400 MHz, CDCl3) δ 4.00 (s, 3H), 7.01 (s, 1H), 7.05 (dd, J=8.4, 0.9 Hz, 1H), 7.11 (ddd, J=7.8, 7.4, 1.1 Hz, 1H), 7.48 (ddd, J=8.4, 7.4, 1.8 Hz, 1H), 8.00 (dd, J=7.8, 1.7 Hz, 1H). was refluxed under nitrogen for 3 hours The reaction was concentrated in vacuo treated with water (30 mL) extracted with dichloromethane (3×10 mL) The combined organic layers were dried over sodium sulfate concentrated in vacuo Purification via silica gel chromatography (Gradient: 0% to 20% ethyl acetate in heptanes)

反应条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of sodium hydride (60% in mineral oil, 202 mg, 8.0 mmol) in 1,2-dimethoxyethane (4 mL) was added drop-wise ethyl trifluoroacetate (954 μL, 8.0 mmol) followed by 1-(2-methoxyphenyl)ethanone (552 μL, 4.0 mmol) and the reaction was heated to 160° C. in a microwave for 15 minutes. Aqueous hydrochloric acid (1 N, 20 mL) was added and the mixture was extracted with tert-butyl methyl ether (3×10 mL). The combined organic layers were dried over sodium sulfate and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 0% to 10% tert-butyl methyl ether in heptanes) afforded the title compound as a red solid. Yield: 933 mg, 3.79 mmol, 95%. GCMS m/z 246 (M+). 1H NMR (400 MHz, CDCl3) δ 3.96 (s, 3H), 6.99 (s, 1H), 7.02 (br d, J=8.5 Hz, 1H), 7.08 (ddd, J=8, 7, 1.0 Hz, 1H), 7.55 (ddd, J=8.4, 7.4, 1.8 Hz, 1H), 7.99 (dd, J=7.9, 1.9 Hz, 1H). the mixture was extracted with tert-butyl methyl ether (3×10 mL) The combined organic layers were dried over sodium sulfate concentrated in vacuo Purification via silica gel chromatography (Gradient: 0% to 10% tert-butyl methyl ether in heptanes)