N-methoxy-N-methyl-2-(2,3,5-trifluorophenyl)acetamide

反応条件: temp:47.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of CeCl3 (11.44 g, 0.045 mol) in THF (350 mL) was degassed for 1 h and heated to 45-50° C. for 5 h. When the solution was cooled to −10-5° C., MeMgCl (19.44 g, 0.26 mol) in THF was added and the mixture was stirred for 1 h at −10-5° C. After amide 43 (30.3 g, 0.13 mol) was charged into the reaction mixture at −10-5° C., the mixture was stirred for 5 h at 10-20° C. After the reaction was complete, the mixture was quenched by 1M HCl, and then partitioned with water and EtOAc. The organic phase was dried over Na2SO4 and concentrated. The crude residual was further purified by flash chromatography on silica gel (2-10% EtOAc/PE) to give 44 (20.8 g, 85% yield). 1H NMR (CDCl3, 400 MHz): δ 6.91-6.78 (m, 1H), 6.69 (dd, 1H), 3.77 (d, 2H), 2.25 (s, 3H); MS (ESI) m/e [M+H]+: 189.05. When the solution was cooled to −10-5° C. the mixture was stirred for 5 h at 10-20° C the mixture was quenched by 1M HCl partitioned with water and EtOAc The organic phase was dried over Na2SO4 concentrated The crude residual was further purified by flash chromatography on silica gel (2-10% EtOAc/PE)

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of NHMe(OMe).HCl (20.3 g, 0.21 mol) in THF (110 mL), H2O (40 mL) and TEA (26.3 g, 0.22 mol) was added 2,3,5-trifluorophenylacetic acid (42, 24.7 g, 0.13 mol) and CDI (24.3 g, 0.15 mol) at 0-10° C. The reaction mixture was stirred at 0-10° C. for 5 h. After HPLC showed that the reaction was complete, the mixture was filtered through celite and the filtrate was partitioned with water and EtOAc. The organic solution was dried over Na2SO4 and concentrated. The crude residual was further purified by flash chromatography on silica gel (5-10% EtOAc/PE) to give 43 (24.0 g, 80% yield). 1H NMR (CDCl3, 400 MHz): δ 6.76-6.72 (m, 2H), 3.72 (m, 2H), 3.66 (d, 3H), 3.15 (d, 3H); MS (ESI) m/e [M+H]+: 234.07. the mixture was filtered through celite the filtrate was partitioned with water and EtOAc The organic solution was dried over Na2SO4 concentrated The crude residual was further purified by flash chromatography on silica gel (5-10% EtOAc/PE)

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of NHMe(OMe).HCl (20.3 g, 0.21 mol) in THF (110 mL), H2O (40 mL) and TEA (26.3 g, 0.22 mol) was added 2,3,5-trifluorophenylacetic acid (42, 24.7 g, 0.13 mol) and CDI (24.3 g, 0.15 mol) at 0-10° C. The reaction mixture was stirred at 0-10° C. for 5 h. After HPLC showed that the reaction was complete, the mixture was filtered through celite and the filtrate was partitioned with water and EtOAc. The organic solution was dried over Na2SO4 and concentrated. The crude residual was further purified by flash chromatography on silica gel (5-10% EtOAc/PE) to give 43 (24.0 g, 80% yield). 1H NMR (CDCl3, 400 MHz): δ 6.76-6.72 (m, 2H), 3.72 (m, 2H), 3.66 (d, 3H), 3.15 (d, 3H); MS (ESI) m/e [M+H]+: 234.07. the mixture was filtered through celite the filtrate was partitioned with water and EtOAc The organic solution was dried over Na2SO4 concentrated The crude residual was further purified by flash chromatography on silica gel (5-10% EtOAc/PE)

反応条件: temp:47.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of CeCl3 (11.44 g, 0.045 mol) in THF (350 mL) was degassed for 1 h and heated to 45-50° C. for 5 h. When the solution was cooled to −10-5° C., MeMgCl (19.44 g, 0.26 mol) in THF was added and the mixture was stirred for 1 h at −10-5° C. After amide 43 (30.3 g, 0.13 mol) was charged into the reaction mixture at −10-5° C., the mixture was stirred for 5 h at 10-20° C. After the reaction was complete, the mixture was quenched by 1M HCl, and then partitioned with water and EtOAc. The organic phase was dried over Na2SO4 and concentrated. The crude residual was further purified by flash chromatography on silica gel (2-10% EtOAc/PE) to give 44 (20.8 g, 85% yield). 1H NMR (CDCl3, 400 MHz): δ 6.91-6.78 (m, 1H), 6.69 (dd, 1H), 3.77 (d, 2H), 2.25 (s, 3H); MS (ESI) m/e [M+H]+: 189.05. When the solution was cooled to −10-5° C. the mixture was stirred for 5 h at 10-20° C the mixture was quenched by 1M HCl partitioned with water and EtOAc The organic phase was dried over Na2SO4 concentrated The crude residual was further purified by flash chromatography on silica gel (2-10% EtOAc/PE)

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of NHMe(OMe).HCl (20.3 g, 0.21 mol) in THF (110 mL), H2O (40 mL) and TEA (26.3 g, 0.22 mol) was added 2,3,5-trifluorophenylacetic acid (42, 24.7 g, 0.13 mol) and CDI (24.3 g, 0.15 mol) at 0-10° C. The reaction mixture was stirred at 0-10° C. for 5 h. After HPLC showed that the reaction was complete, the mixture was filtered through celite and the filtrate was partitioned with water and EtOAc. The organic solution was dried over Na2SO4 and concentrated. The crude residual was further purified by flash chromatography on silica gel (5-10% EtOAc/PE) to give 43 (24.0 g, 80% yield). 1H NMR (CDCl3, 400 MHz): δ 6.76-6.72 (m, 2H), 3.72 (m, 2H), 3.66 (d, 3H), 3.15 (d, 3H); MS (ESI) m/e [M+H]+: 234.07. the mixture was filtered through celite the filtrate was partitioned with water and EtOAc The organic solution was dried over Na2SO4 concentrated The crude residual was further purified by flash chromatography on silica gel (5-10% EtOAc/PE)