(2,6-dibromophenyl)methyl acetate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a cooled (dry ice-acetone bath) mixture of 2,6-dibromo-benzyl acetate (5.05 g, 16.4 mmol) and PdCl2(dppf) (0.08 eq) in dry THF (50 mL) was added 1.1 M Et2Zn (60 mL, 66 mmol, 4 eq). The resulting mixture was allowed to warm to RT, stirred at 45° C. (programmed block temperature, ˜40 h), and added to a stirred mixture of dilute HCl and heptane/EtOAc. The organic layer was dried (Na2SO4), filtered, and evaporated. Chromatography (2%-10% EtOAc/heptane stepwise gradient) gave 2.12 g (yield of 63%) of the title product, along with 0.20 g of 2,6-diethylbenzyl alcohol. 1H NMR (300 MHz, CDCl3) δ 1.21 (t, 6H), 2.07 (s, 3H), 2.70 (q, 4H), 5.19 (s, 2H), 7.09 (d, 2H), 7.22 (dd, 1H). The following compound was prepared by making appropriate substitutions to the above procedure: To a cooled The organic layer was dried (Na2SO4) filtered evaporated

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1,3-dibromo-2-(bromomethyl)benzene (27.6 g, 84 mmol), NaOAc (35.5 g, 5 eq.) and dimethylformamide (DMF) (150 mL) was stirred at 100° C. (hot oil bath temperature) for 1.75 h, allowed to cool, and then partitioned between heptane (500 mL) and water (200 mL). After removing the organic layer, the aqueous layer was extracted with heptane (200 mL). The combined organics were washed with H2O (2×300 mL), dried (Na2SO4), filtered, and evaporated to give 24.57 g (yield of 95%) of title product as a colorless oil. This oil contained 13% unreacted starting material but was successfully used without further purification. 1H NMR (300 MHz, CDCl3) δ 2.10 (s, 3H), 5.41 (s, 2H), 7.08 (t, 1H), 7.58 (d, 2H). to cool partitioned between heptane (500 mL) and water (200 mL) After removing the organic layer the aqueous layer was extracted with heptane (200 mL) The combined organics were washed with H2O (2×300 mL) dried (Na2SO4) filtered evaporated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To the solution of 1,3-dibromo-2-bromomethylbenzene (71.3 g) in DMF (300 mL) was added sodium acetate (91.7 g) and the resulting mixture was stirred at 105° C. for 6 h. The mixture was cooled and quenched with water (1500 mL) and extracted with ethyl acetate (1000 mL×2). The combined organic layers were washed with water (1000 mL) and brine (1000 mL), dried over anhydrous sodium sulfate and filtered. The residue was purified by silica gel column (200-300 mesh, eluting with petroleum ether/ethyl acetate 30/1) to give acetic acid 2,6-dibromobenzyl ester as a yellow oil (59.42 g, yield 89%). 1H NMR (300 MHz, d6-DMSO) δ 7.57 (d, J=8.0 Hz, 2H), 7.07 (t, J=7.8 Hz, 1H), 5.41 (s, 2H), 2.11 (s, 3H). The mixture was cooled quenched with water (1500 mL) extracted with ethyl acetate (1000 mL×2) The combined organic layers were washed with water (1000 mL) and brine (1000 mL) dried over anhydrous sodium sulfate filtered The residue was purified by silica gel column (200-300 mesh, eluting with petroleum ether/ethyl acetate 30/1)

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet was charged with 106c (390 mg, 2.05 mmol), 102d (1.26 g, 4.10 mmol), cesium carbonate (1.34 g, 4.10 mmol), N,N′-dimethylethylenediamine (181 mg, 2.05 mmol) and 1,4-dioxane (12 mL). After bubbling nitrogen through the resulting suspension for 30 min, copper iodide (195 mg, 1.03 mmol) was added. A reflux condenser was attached to the flask, and the reaction mixture was heated at 105° C. for 16 h. After this time, the mixture was cooled to room temperature and filtered. The filtrate was diluted with ethyl acetate (150 mL) and water (75 mL), and the layers were separated. The aqueous layer was extracted with ethyl acetate (2×50 mL), and the combined organic layers were washed with brine (100 mL) and dried over sodium sulfate. The drying agent was removed by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by flash column chromatography (silica, 70:30 hexanes/ethyl acetate) to afford 106d in 50% yield (427 mg) as a white solid: mp 97-99° C.; 1H NMR (500 MHz, CDCl3) δ 7.74 (d, J=8.5 Hz, 1H), 7.63 (dd, J=8.0, 1.5 Hz, 1H), 7.30-7.25 (m, 2H), 6.80 (dd, J=8.5, 2.0 Hz, 1H), 6.66 (d, J=1.5 Hz, 1H), 5.21 (s, 2H), 4.69 (s, 2H), 3.51 (q, J=7.0 Hz, 2H), 3.21 (s, 3H), 1.99 (s, 3H), 1.19 (t, J=7.0 Hz, 3H); MS (ESI+) m/z 417.1 (M+H). A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet After bubbling nitrogen through the resulting suspension for 30 min A reflux condenser was attached to the flask After this time, the mixture was cooled to room temperature filtered The filtrate was diluted with ethyl acetate (150 mL) and water (75 mL) the layers were separated The aqueous layer was extracted with ethyl acetate (2×50 mL) the combined organic layers were washed with brine (100 mL) dried over sodium sulfate The drying agent was removed by filtration The filtrate was concentrated under reduced pressure the resulting residue was purified by flash column chromatography (silica, 70:30 hexanes/ethyl acetate)

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 100-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer was purged with nitrogen and charged with 102c (570 mg, 3.02 mmol), 102d (1.85 g, 6.04 mmol), cesium carbonate (1.96 g, 6.04 mmol), N,N′-dimethyl-ethylenediamine (266 mg, 3.02 mmol), and 1,4-dioxane (27 mL). After bubbling nitrogen through the resulting suspension for 30 min, copper iodide (287 mg, 1.51 mmol) was added, and the reaction mixture was heated at 105° C. (oil bath temperature) for 14 h. After this time, the mixture was cooled to room temperature and filtered. The filtrate was diluted with ethyl acetate (150 mL) and water (30 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica, 0% to 50% ethyl acetate/hexanes) to afford a 41% yield (555 mg) of 102e as an off-white solid: mp 176-178° C.; 1H NMR (300 MHz, CDCl3) δ 7.86 (d, 1H, J=8.1 Hz), 7.66 (dd, 1H, J=7.9, 1.5 Hz), 7.59 (dd, 1H, J=8.1, 1.5 Hz), 7.52 (s, 1H), 7.29 (m, 2H), 5.20 (s, 2H), 4.77 (s, 2H), 1.99 (s, 3H), 1.40 (s, 9H); MS (ESI+) m/z 416.1 (M+H). A 100-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer was purged with nitrogen After bubbling nitrogen through the resulting suspension for 30 min After this time, the mixture was cooled to room temperature filtered The filtrate was diluted with ethyl acetate (150 mL) and water (30 mL) The organic layer was separated the aqueous layer was extracted with ethyl acetate (3×50 mL) The combined organic layers were dried over sodium sulfate concentrated under reduced pressure The residue was purified by column chromatography (silica, 0% to 50% ethyl acetate/hexanes)

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 100-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer was purged with nitrogen and charged with 102c (570 mg, 3.02 mmol), 102d (1.85 g, 6.04 mmol), cesium carbonate (1.96 g, 6.04 mmol), N,N′-dimethyl-ethylenediamine (266 mg, 3.02 mmol), and 1,4-dioxane (27 mL). After bubbling nitrogen through the resulting suspension for 30 min, copper iodide (287 mg, 1.51 mmol) was added, and the reaction mixture was heated at 105° C. (oil bath temperature) for 14 h. After this time, the mixture was cooled to room temperature and filtered. The filtrate was diluted with ethyl acetate (150 mL) and water (30 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica, 0% to 50% ethyl acetate/hexanes) to afford a 41% yield (555 mg) of 102e as an off-white solid: mp 176-178° C.; 1H NMR (300 MHz, CDCl3) δ 7.86 (d, 1H, J=8.1 Hz), 7.66 (dd, 1H, J=7.9, 1.5 Hz), 7.59 (dd, 1H, J=8.1, 1.5 Hz), 7.52 (s, 1H), 7.29 (m, 2H), 5.20 (s, 2H), 4.77 (s, 2H), 1.99 (s, 3H), 1.40 (s, 9H); MS (ESI+) m/z 416.1 (M+H). A 100-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer was purged with nitrogen After bubbling nitrogen through the resulting suspension for 30 min After this time, the mixture was cooled to room temperature filtered The filtrate was diluted with ethyl acetate (150 mL) and water (30 mL) The organic layer was separated the aqueous layer was extracted with ethyl acetate (3×50 mL) The combined organic layers were dried over sodium sulfate concentrated under reduced pressure The residue was purified by column chromatography (silica, 0% to 50% ethyl acetate/hexanes)