2-(2-hydroxy-3-methoxyphenyl)acetonitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-hydroxy-3-methoxyphenylacetonitrile (1 g, 6.1 mmol) in DMF (12 mL) was added 1,1-dimethylethyl 4-{[(methylsulfonyl)oxy]methyl}piperidine-1-carboxylate (1.8 g, 6.1 mmol) and cesium carbonate (4.0 g, 12.2 mmol). The mixture was heated to 70° C. for 3 h and then cooled to rt. Water and ethyl acetate were added followed by brine to reduce emulsification. The layers were partitioned, and the aqueous phase was extracted with ethyl acetate. The organic extracts were combined, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (70% hexanes, 30% ethyl acetate) to provide 1.77 g of 1,1-dimethylethyl 4-({[2-(cyanomethyl)-6-(methyloxy)phenyl]oxy}methyl)piperidine-1-carboxylate (4.9 mmol, 81% yield) as a yellow syrup. 1H NMR (400 MHz, CDCl3): δ7.03 (t, 1H), 6.93 (dd, 1H), 6.88 (dd, 1H), 4.14 (br m, 2H), 3.88 (br d, 2H), 3.84 (s, 3H), 3.70 (s, 2H), 2.00 (m, 1H), 1.86 (br d, 2H), 1.47 (s, 9H), 1.35-1.25 (m, 2H). cooled to rt The layers were partitioned the aqueous phase was extracted with ethyl acetate dried over sodium sulfate filtered concentrated in vacuo The residue was purified by flash chromatography (70% hexanes, 30% ethyl acetate)

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-hydroxy-3-methoxyphenylacetonitrile (1 g, 6.1 mmol) in DMF (12 mL) was added 1,1-dimethylethyl 4-{[(methylsulfonyl)oxy]methyl}piperidine-1-carboxylate (1.8 g, 6.1 mmol) and cesium carbonate (4.0 g, 12.2 mmol). The mixture was heated to 70° C. for 3 h and then cooled to rt. Water and ethyl acetate were added followed by brine to reduce emulsification. The layers were partitioned, and the aqueous phase was extracted with ethyl acetate. The organic extracts were combined, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (70% hexanes, 30% ethyl acetate) to provide 1.77 g of 1,1-dimethylethyl 4-({[2-(cyanomethyl)-6-(methyloxy)phenyl]oxy}methyl)piperidine-1-carboxylate (4.9 mmol, 81% yield) as a yellow syrup. 1H NMR (400 MHz, CDCl3): δ7.03 (t, 1H), 6.93 (dd, 1H), 6.88 (dd, 1H), 4.14 (br m, 2H), 3.88 (br d, 2H), 3.84 (s, 3H), 3.70 (s, 2H), 2.00 (m, 1H), 1.86 (br d, 2H), 1.47 (s, 9H), 1.35-1.25 (m, 2H). cooled to rt The layers were partitioned the aqueous phase was extracted with ethyl acetate dried over sodium sulfate filtered concentrated in vacuo The residue was purified by flash chromatography (70% hexanes, 30% ethyl acetate)

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-hydroxy-3-methoxyphenylacetonitrile (1 g, 6.1 mmol) in DMF (12 mL) was added 1,1-dimethylethyl 4-{[(methylsulfonyl)oxy]methyl}piperidine-1-carboxylate (1.8 g, 6.1 mmol) and cesium carbonate (4.0 g, 12.2 mmol). The mixture was heated to 70° C. for 3 h and then cooled to rt. Water and ethyl acetate were added followed by brine to reduce emulsification. The layers were partitioned, and the aqueous phase was extracted with ethyl acetate. The organic extracts were combined, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (70% hexanes, 30% ethyl acetate) to provide 1.77 g of 1,1-dimethylethyl 4-({[2-(cyanomethyl)-6-(methyloxy)phenyl]oxy}methyl)piperidine-1-carboxylate (4.9 mmol, 81% yield) as a yellow syrup. 1H NMR (400 MHz, CDCl3): δ7.03 (t, 1H), 6.93 (dd, 1H), 6.88 (dd, 1H), 4.14 (br m, 2H), 3.88 (br d, 2H), 3.84 (s, 3H), 3.70 (s, 2H), 2.00 (m, 1H), 1.86 (br d, 2H), 1.47 (s, 9H), 1.35-1.25 (m, 2H). cooled to rt The layers were partitioned the aqueous phase was extracted with ethyl acetate dried over sodium sulfate filtered concentrated in vacuo The residue was purified by flash chromatography (70% hexanes, 30% ethyl acetate)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-hydroxy-3-methoxyphenylacetonitrile (1 g, 6.1 mmol) in DMF (12 mL) was added 1,1-dimethylethyl 4-{[(methylsulfonyl)oxy]methyl}piperidine-1-carboxylate (1.8 g, 6.1 mmol) and cesium carbonate (4.0 g, 12.2 mmol). The mixture was heated to 70° C. for 3 h and then cooled to rt. Water and ethyl acetate were added followed by brine to reduce emulsification. The layers were partitioned, and the aqueous phase was extracted with ethyl acetate. The organic extracts were combined, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (70% hexanes, 30% ethyl acetate) to provide 1.77 g of 1,1-dimethylethyl 4-({[2-(cyanomethyl)-6-(methyloxy)phenyl]oxy}methyl)piperidine-1-carboxylate (4.9 mmol, 81% yield) as a yellow syrup. 1H NMR (400 MHz, CDCl3): δ7.03 (t, 1H), 6.93 (dd, 1H), 6.88 (dd, 1H), 4.14 (br m, 2H), 3.88 (br d, 2H), 3.84 (s, 3H), 3.70 (s, 2H), 2.00 (m, 1H), 1.86 (br d, 2H), 1.47 (s, 9H), 1.35-1.25 (m, 2H). cooled to rt The layers were partitioned the aqueous phase was extracted with ethyl acetate dried over sodium sulfate filtered concentrated in vacuo The residue was purified by flash chromatography (70% hexanes, 30% ethyl acetate)