ethyl 2-fluoro-4-iodobenzoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2.5 g (27.0 mmol) of 2-fluoro-4-iodobenzoic acid (Compound B) in 11 mL (8.6 g, 187.5 mmol) of ethanol was added 0.3 mL of c. sulfuric acid. The reaction mixture was heated to reflux in an oil bath (90° C.) for 1.75 hours, fitted with a short path distillation apparatus, distilled and then allowed to cool to ambient temperature. The reaction mixture was extracted and partitioned between pentane and water and the layers were separated. The aqueous phase was washed with pentane and the organic phases were combined. The combined organic phase was washed sequentially with sat. NaHCO3 (aq.) solution, water and brine, dried over MgSO4, filtered and concentrated in vacuo to a purple oil. Purification by flash chromatography (silica, 10% ethyl acetate in hexane) gave the title compound as an orange oil. PMR (CDCl3): δ 1.39 (3 H, t, J=7.1 Hz), 4.39 (2 H, q, J=7.1 Hz), 7.52-7.67 (3 H, m). The reaction mixture was heated fitted with a short path distillation apparatus distilled to cool to ambient temperature The reaction mixture was extracted partitioned between pentane and water the layers were separated The aqueous phase was washed with pentane The combined organic phase was washed sequentially with sat. NaHCO3 (aq.) solution, water and brine dried over MgSO4 filtered concentrated in vacuo to a purple oil Purification by flash chromatography (silica, 10% ethyl acetate in hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 6-ethynyl-2,2-dimethylchroman-4-one (Compound 262, 314.0 mg, 1.57 mmol) and ethyl 2-fluoro-4-iodobenzoate (440.0 mg, 1.50 mmol) in 10.0 mL Et3N was purged with argon for 15 minutes. To this solution was added bis(triphenylphosphine)-palladium(II) chloride (275.0 mg, 0.39 mmol) and copper(I) iodide (75.0 mg, 0.39 mmol). After sparging for an additional 10 minutes with argon, the solution was stirred overnight at room temperature. The reaction mixture was filtered through a pad of Celite using an Et2O wash. Concentration of the filtrate under reduced pressure, followed by column chromatography (3-5% EtOAc-hexanes) of the residual solid afforded 400.0 mg (69%) the title compound as an orange solid. 1H NMR (300 MHz, CDCl3) δ: 8.05 (1H, d, J=2.1 Hz), 7.90 (1H, d, J=7.8 Hz), 7.60 (1H, dd, J=2.2 8.5 Hz), 7.29 (1H, dd, J=1.5, 8.2 Hz), 7.25 (1H, d, J=11.4 Hz), 6.93 (1H, d, J=8.5 Hz), 4.39 (2H, q, J=7.1 Hz), 2.75 (2H, s), 1.48 (6H, s), 1.40 (3H, t, J=7.1 Hz). After sparging for an additional 10 minutes with argon The reaction mixture was filtered through a pad of Celite wash

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2.5 g (27.0 mmol) of 2-fluoro-4-iodobenzoic acid (Compound B) in 11 mL (8.6 g, 187.5 mmol) of ethanol was added 0.3 mL of c. sulfuric acid. The reaction mixture was heated to reflux in an oil bath (90° C.) for 1.75 hours, fitted with a short path distillation apparatus, distilled and then allowed to cool to ambient temperature. The reaction mixture was extracted and partitioned between pentane and water and the layers were separated. The aqueous phase was washed with pentane and the organic phases were combined. The combined organic phase was washed sequentially with sat. NaHCO3 (aq.) solution, water and brine, dried over MgSO4, filtered and concentrated in vacuo to a purple oil. Purification by flash chromatography (silica, 10% ethyl acetate in hexane) gave the title compound as an orange oil. The reaction mixture was heated fitted with a short path distillation apparatus distilled to cool to ambient temperature The reaction mixture was extracted partitioned between pentane and water the layers were separated The aqueous phase was washed with pentane The combined organic phase was washed sequentially with sat. NaHCO3 (aq.) solution, water and brine dried over MgSO4 filtered concentrated in vacuo to a purple oil Purification by flash chromatography (silica, 10% ethyl acetate in hexane)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2.5 g (27.0 mmol) of 2-fluoro-4-iodobenzoic acid (Compound B) in 11 mL (8.6 g, 187.5 mmol) of ethanol was added 0.3 mL of c. sulfuric acid. The reaction mixture was heated to reflux in an oil bath (90° C.) for 1.75 hours, fitted with a short path distillation apparatus, distilled and then allowed to cool to ambient temperature. The reaction mixture was extracted and partitioned between pentane and water and the layers were separated. The aqueous phase was washed with pentane and the organic phases were combined. The combined organic phase was washed sequentially with sat. NaHCO3 (aq.) solution, water and brine, dried over MgSO4, filtered and concentrated in vacuo to a purple oil. Purification by flash chromatography (silica, 10% ethyl acetate in hexane) gave the title compound as an orange oil. The reaction mixture was heated fitted with a short path distillation apparatus distilled to cool to ambient temperature The reaction mixture was extracted partitioned between pentane and water the layers were separated The aqueous phase was washed with pentane The combined organic phase was washed sequentially with sat. NaHCO3 (aq.) solution, water and brine dried over MgSO4 filtered concentrated in vacuo to a purple oil Purification by flash chromatography (silica, 10% ethyl acetate in hexane)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2.5 g (27.0 mmol) of 2-fluoro-4-iodobenzoic acid (Compound B) in 11 mL (8.6 g, 187.5 mmol) of ethanol was added 0.3 mL of c. sulfuric acid. The reaction mixture was heated to reflux in an oil bath (90° C.) for 1.75 hours, fitted with a short path distillation apparatus, distilled and then allowed to cool to ambient temperature. The reaction mixture was extracted and partitioned between pentane and water and the layers were separated. The aqueous phase was washed with pentane and the organic phases were combined. The combined organic phase was washed sequentially with sat. NaHCO3 (aq.) solution, water and brine, dried over MgSO4, filtered and concentrated in vacuo to a purple oil. Purification by flash chromatography (silica, 10% ethyl acetate in hexane) gave the title compound as an orange oil. The reaction mixture was heated fitted with a short path distillation apparatus distilled to cool to ambient temperature The reaction mixture was extracted partitioned between pentane and water the layers were separated The aqueous phase was washed with pentane The combined organic phase was washed sequentially with sat. NaHCO3 (aq.) solution, water and brine dried over MgSO4 filtered concentrated in vacuo to a purple oil Purification by flash chromatography (silica, 10% ethyl acetate in hexane)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 25 g (27.0 mmol) of 2-fluoro-4-iodobenzoic acid (Compound B) in 11 mL (8.6 g, 187.5 mmol) of ethanol was added 0.3 mL of c. sulfuric acid. The reaction mixture was heated to reflux in an oil bath (90° C.) for 1.75 hours, fitted with a short path distillation apparatus, distilled and then allowed to cool to ambient temperature. The reaction mixture was extracted and partitioned between pentane and water and the layers were separated. The aqueous phase was washed with pentane and the organic phases were combined. The combined organic phase was washed sequentially with sat. NaHCO3 (aq.) solution, water and brine, dried over MgSO4, filtered and concentrated in vacuo to a purple oil. Purification by flash chromatography (silica, 10% ethyl acetate in hexane) gave the title compound as an orange oil. The reaction mixture was heated fitted with a short path distillation apparatus distilled to cool to ambient temperature The reaction mixture was extracted partitioned between pentane and water the layers were separated The aqueous phase was washed with pentane The combined organic phase was washed sequentially with sat. NaHCO3 (aq.) solution, water and brine dried over MgSO4 filtered concentrated in vacuo to a purple oil Purification by flash chromatography (silica, 10% ethyl acetate in hexane)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2.5 g (27.0 mmol) of 2-fluoro-4-iodobenzoic acid (Compound B) in 11 mL (8.6 g, 187.5 mmol) of ethanol was added 0.3 mL of c. sulfuric acid. The reaction mixture was heated to reflux in an oil bath (90° C.) for 1.75 hours, fitted with a short path distillation apparatus, distilled and then allowed to cool to ambient temperature. The reaction mixture was extracted and partitioned between pentane and water and the layers were separated. The aqueous phase was washed with pentane and the organic phases were combined. The combined organic phase was washed sequentially with sat. NaHCO3 (aq.) solution, water and brine, dried over MgSO4, filtered and concentrated in vacuo to a purple oil. Purification by flash chromatography (silica, 10% ethyl acetate in hexane) gave the title compound as an orange oil. The reaction mixture was heated fitted with a short path distillation apparatus distilled to cool to ambient temperature The reaction mixture was extracted partitioned between pentane and water the layers were separated The aqueous phase was washed with pentane The combined organic phase was washed sequentially with sat. NaHCO3 (aq.) solution, water and brine dried over MgSO4 filtered concentrated in vacuo to a purple oil Purification by flash chromatography (silica, 10% ethyl acetate in hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 0.20 g (0.72 mmol) of 4,4-dimethyl-1,2,3,4-tetrahydro-N-(4-methylphenyl)-7-ethynylquinoline (Compound 3) and 0.39 g (1.5 mmol) of ethyl 2-fluoro-4-iodobenzoate were added 2.9 g (4.0 mL, 29 mmol) of triethylamine, 0.029 g (0.15 mmol) of copper(I) iodide, and 0.113 g (0.16 mmol) of bis(triphenylphosphine)palladium(II) chloride, consecutively. The resulting mixture was stirred at room temperature for 20 hours. Methylene chloride was added and the reaction was adsorbed onto silica gel. The product was obtained by flash chromatography (5% ethyl acetate in hexanes) followed by recrystallization in ethanol to give the title compound as orange crystals. PNMR (300 MHz, CDCl3) d 1.37 (6 H, s), 1.40 (3 H, t, J=7.1 Hz), 1.86 (2 H, t, J=6.0 Hz), 2.38 (3 H, s), 3.61 (2 H, t, J=6.0 Hz), 4.39 (2 H, q, J=7.1 Hz), 6.77 (1 H, d, J=1.7 Hz), 6.87 (1 H, dd, J=7.9, 1.7 Hz), 7.23-7.28 (7 H, m), 7.86 (1 H, t, J=7.8 Hz). followed by recrystallization in ethanol

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2.5 g (27.0 mmol) of 2-fluoro-4-iodobenzoic acid (Compound B) in 11 mL (8.6 g, 187.5 mmol) of ethanol was added 0.3 mL of c. sulfuric acid. The reaction mixture was heated to reflux in an oil bath (90° C.) for 1.75 hours, fitted with a short path distillation apparatus, distilled and then allowed to cool to ambient temperature. The reaction mixture was extracted and partitioned between pentane and water and the layers were separated. The aqueous phase was washed with pentane and the organic phases were combined. The combined organic phase was washed sequentially with sat. NaHCO3 (aq.) solution, water and brine, dried over MgSO4, filtered and concentrated in vacuo to a purple oil. Purification by flash chromatography (silica, 10% ethyl acetate in hexane) gave the title compound as an orange oil. The reaction mixture was heated fitted with a short path distillation apparatus distilled to cool to ambient temperature The reaction mixture was extracted partitioned between pentane and water the layers were separated The aqueous phase was washed with pentane The combined organic phase was washed sequentially with sat. NaHCO3 (aq.) solution, water and brine dried over MgSO4 filtered concentrated in vacuo to a purple oil Purification by flash chromatography (silica, 10% ethyl acetate in hexane)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2.5 g (27.0 mmol) of 2-fluoro-4-iodobenzoic acid (Compound B) in 11 mL (8.6 g, 187.5 mmol) of ethanol was added 0.3 mL of c. sulfuric acid. The reaction mixture was heated to reflux in an oil bath (90° C.) for 1.75 hours, fitted with a short path distillation apparatus, distilled and then allowed to cool to ambient temperature. The reaction mixture was extracted and partitioned between pentane and water and the layers were separated. The aqueous phase was washed with pentane and the organic phases were combined. The combined organic phase was washed sequentially with sat. NaHCO3 (aq.) solution, water and brine, dried over MgSO4, filtered and concentrated in vacuo to a purple oil. Purification by flash chromatography (silica, 10% ethyl acetate in hexane) gave the title compound as an orange oil. PMR (CDCl3): δ 1.39 (3 H, t, J=7.1 Hz), 4.39 (2 H, q, J=7.1 Hz), 7.52-7.67 (3 H, m). The reaction mixture was heated fitted with a short path distillation apparatus distilled to cool to ambient temperature The reaction mixture was extracted partitioned between pentane and water the layers were separated The aqueous phase was washed with pentane The combined organic phase was washed sequentially with sat. NaHCO3 (aq.) solution, water and brine dried over MgSO4 filtered concentrated in vacuo to a purple oil Purification by flash chromatography (silica, 10% ethyl acetate in hexane)