3-(4-bromophenyl)-N-methoxy-N-methylpropanamide

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 solution of 25.02 g 3-(4-Bromophenyl)-N-methoxy-N-methylpropanamide from Step A above in 500 mL anhydrous ether cooled in an ice bath was added 115 mL 2 M cyclohexylmagnesium bromide in ether over 30 minutes. The cooling bath was removed after finishing addition. After 75 minutes, an additional 30 mL 2 M cyclohexylmagnesium bromide in ether was added. The reaction mixture was stirred for 40 minutes and poured into a mixture containing 500 mL ether, 500 mL cold water, 200 mL saturated brine, and 175 mL 2 N HCl. The layers were separated. The aqueous layer was extracted with 4×75 mL ether. The combined ether solution was washed with 200 mL 1:1 5% NaHCO3 and saturated brine followed by 200 mL saturated brine, dried over anhydrous Na2SO4, and evaporated to give a crude product. It was purified on silica gel using 20-100% EtOAc in hexanes and re-purified using 5-10% EtOAc in hexanes to give the title compound as yellow oil. 1H NMR (CDCl3, 500 MHz) δ 7.39˜7.42 (m, 2H), 7.06˜7.09 (m, 2H), 2.84˜2.87 (m, 2H), 2.74˜2.78 (m, 2H), 2.32 (tt, J=3.3 & 11.3 Hz, 1H), 1.76˜1.84 (m, 4H), 1.65˜1.70 (m, 1H), 1.15˜1.36 (m, 5H). The cooling bath was removed addition an additional 30 mL 2 M cyclohexylmagnesium bromide in ether was added poured into a mixture containing 500 mL ether, 500 mL cold water, 200 mL saturated brine, and 175 mL 2 N HCl The layers were separated The aqueous layer was extracted with 4×75 mL ether The combined ether solution was washed with 200 mL 1:1 5% NaHCO3 and saturated brine dried over anhydrous Na2SO4 evaporated to give a crude product It was purified on silica gel using 20-100% EtOAc in hexanes re-purified

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

実験手順: To a mixture of 24.95 g 3-(4-bromophenyl)propionic acid, 12.75 g N,O-dimethylhydroxylamine hydrochloride, 27.14 g EDC, and 17.66 g HOBt were added 300 mL DMF and 47.4 mL DIEA. The reaction mixture was stirred at room temperature for 17 hours and then poured into 700 mL ice water, extracted with 5×200 mL EtOAc. The combined EtOAc solution was washed with 200 mL 5% NaHCO3, 4×200 mL water, and 200 mL saturated brine, dried over Na2SO4, and concentrated under reduced pressure to give crude product as a yellow oil. It was purified on silica gel using 35-55% EtOAc in hexanes to give the title compound as yellowish oil. 1H NMR (CDCl3, 500 MHz) δ 7.40˜7.43 (m, 2H), 7.11˜7.14 (m, 2H), 3.63 (s, 3), 3.19 (s, 3H), 2.93 (t, J=7.8 Hz, 2H), 2.73 (t, J=7.7 Hz, 2H). LC-MS: 1.77 min. (M+H=272.1/274). extracted with 5×200 mL EtOAc The combined EtOAc solution was washed with 200 mL 5% NaHCO3, 4×200 mL water, and 200 mL saturated brine dried over Na2SO4 concentrated under reduced pressure to give crude product as a yellow oil It was purified on silica gel using 35-55% EtOAc in hexanes

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

実験手順: To a solution of 25.02 g 3-(4-Bromophenyl)-N-methoxy-N-methylpropanamide from Step A above in 500 mL anhydrous ether cooled in an ice bath was added 115 mL 2 M cyclohexylmagnesium bromide in ether over 30 minutes. The cooling bath was removed after finishing addition. After 75 minutes, an additional 30 mL 2 M cyclohexylmagnesium bromide in ether was added. The reaction mixture was stirred for 40 minutes and poured into a mixture containing 500 mL ether, 500 mL cold water, 200 mL saturated brine, and 175 mL 2 N HCl. The layers were separated. The aqueous layer was extracted with 4×75 mL ether. The combined ether solution was washed with 200 mL 1:1 5% NaHCO3 and saturated brine followed by 200 mL saturated brine, dried over anhydrous Na2SO4, and evaporated to give a crude product. It was purified on silica gel using 20˜100% EtOAc in hexanes and re-purified using 5˜10% EtOAc in hexanes to give the title compound as yellow oil. 1H NMR (CDCl3, 500 MHz) δ 7.39˜7.42 (m, 2H), 7.06˜7.09 (m, 2H), 2.84˜2.87 (m, 2H), 2.74˜2.78 (m, 2H), 2.32 (tt, J=3.3 & 11.3 Hz, 1H), 1.76˜1.84 (m, 4H), 1.65˜1.70 (m, 1H), 1.15˜1.36 (m, 5H). The cooling bath was removed addition an additional 30 mL 2 M cyclohexylmagnesium bromide in ether was added poured into a mixture containing 500 mL ether, 500 mL cold water, 200 mL saturated brine, and 175 mL 2 N HCl The layers were separated The aqueous layer was extracted with 4×75 mL ether The combined ether solution was washed with 200 mL 1:1 5% NaHCO3 and saturated brine dried over anhydrous Na2SO4 evaporated to give a crude product It was purified on silica gel using 20˜100% EtOAc in hexanes re-purified

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

実験手順: To a mixture of 24.95 g 3-(4-bromophenyl)propionic acid, 12.75 g N, O-dimethylhydroxylamine hydrochloride, 27.14 g EDC, and 17.66 g HOBt were added 300 mL DMF and 47.4 mL DIEA. The reaction mixture was stirred at room temperature for 17 hours and then poured into 700 mL ice water, extracted with 5×200 mL EtOAc. The combined EtOAc solution was washed with 200 mL 5% NaHCO3, 4×200 mL water, and 200 mL saturated brine, dried over Na2SO4, and concentrated under reduced pressure to give crude product as a yellow oil. It was purified on silica gel using 35˜55% EtOAc in hexanes to give the title compound as yellowish oil. 1H NMR (CDCl3, 500 MHz) δ 7.40˜7.43 (m, 2H), 7.11˜7.14 (m, 2H), 3.63 (s, 3H), 3.19 (s, 3H), 2.93 (t, J=7.8 Hz, 2H), 2.73 (t, J=7.7 Hz, 2H). LC-MS: 1.77 min. (M+H=272.1/274). extracted with 5×200 mL EtOAc The combined EtOAc solution was washed with 200 mL 5% NaHCO3, 4×200 mL water, and 200 mL saturated brine dried over Na2SO4 concentrated under reduced pressure to give crude product as a yellow oil It was purified on silica gel using 35˜55% EtOAc in hexanes