奥沙西泮杂质11

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-amino-3-chlorobenzophenone (0.730 g, 3.15 mmol) and ethyl glycinate hydrochloride salt (0.660 g, 4.72 mmol) in pyridine (15 mL) was refluxed using a Dean-Stark trap to remove water. After 30 h the reaction was cooled and concentrated. The residue was dissolve in methylene chloride and washed with saturated sodium bicarbonate. The crude product was purified by chromatography (silica gel, 0–30% ethyl acetate in hexane gradient elution) to give the title compound as a solid (0.557 g). 1H NMR (500 MHz, CDCl3) δ 7.83 (br s, 1H), 7.61 (dd, J=1, 8 Hz, 1H), 7.52 (m, 2H), 7.46 (tt, J=1,8 Hz, 1H), 7.39 (t, J=8 Hz, 2H), 7.26 (m, 1H), 7.11 (t, J=8 Hz, 1H), 4.36 (br s, 2H). to remove water After 30 h the reaction was cooled concentrated The residue was dissolve in methylene chloride washed with saturated sodium bicarbonate The crude product was purified by chromatography (silica gel, 0–30% ethyl acetate in hexane gradient elution)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Phenylmagnesium bromide (3.11 mL, 3.0 M in ether, 9.34 mmol) was added at room temperature to a solution of 8-chloro-2-methyl-4H-3,1-benzoxazin-4-one (2.15 g, 10.9 mmol) in benzene (10 mL) and tetrahydrofuran (3 mL). The reaction was refluxed for 2h, cooled, and quenched with 2N hydrochloric acid (10 mL). The layers were separated and the organic phase washed with 5% sodium hydroxide, dried over magnesium sulfate, and concentrated. The residue was refluxed in ethanol (12 mL) and 6N hydrochloric acid (6 mL) overnight, then concentrated in vacuo. The residue was dissolved in benzene (30 mL) and treated with 5N ammonium hydroxide (20 mL). The organic extract was dried and concentrated. The crude product was purified by chromatography (silica gel, 0 to 5% ethyl acetate in hexane gradient elution), giving the title compound (0.84 g). 1H NMR (500 MHz, CDCl3) δ 7.63 (d, J=7 Hz, 2H), 7.54 (t, J=7 Hz, 1H), 7.49–7.42 (m, 3H), 7.39 (d, J=8 Hz, 1H), 6.56 (t, J=8 Hz, 1H), 6.58 (br s, 2H). cooled quenched with 2N hydrochloric acid (10 mL) The layers were separated the organic phase washed with 5% sodium hydroxide dried over magnesium sulfate concentrated The residue was refluxed in ethanol (12 mL) 6N hydrochloric acid (6 mL) overnight, then concentrated in vacuo The residue was dissolved in benzene (30 mL) treated with 5N ammonium hydroxide (20 mL) The organic extract was dried concentrated The crude product was purified by chromatography (silica gel, 0 to 5% ethyl acetate in hexane gradient elution)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Phenylmagnesium bromide (3.11 mL, 3.0 M in ether, 9.34 mmol) was added at room temperature to a solution of 8-chloro-2-methyl-4H-3,1-benzoxazin-4-one (2.15 g, 10.9 mmol) in benzene (10 mL) and tetrahydrofuran (3 mL). The reaction was refluxed for 2h, cooled, and quenched with 2N hydrochloric acid (10 mL). The layers were separated and the organic phase washed with 5% sodium hydroxide, dried over magnesium sulfate, and concentrated. The residue was refluxed in ethanol (12 mL) and 6N hydrochloric acid (6 mL) overnight, then concentrated in vacuo. The residue was dissolved in benzene (30 mL) and treated with 5N ammonium hydroxide (20 mL). The organic extract was dried and concentrated. The crude product was purified by chromatography (silica gel, 0 to 5% ethyl acetate in hexane gradient elution), giving the title compound (0.84 g). 1H NMR (500 MHz, CDCl3) δ 7.63 (d, J=7 Hz, 2H), 7.54 (t, J=7 Hz, 1H), 7.49–7.42 (m, 3H), 7.39 (d, J=8 Hz, 1H), 6.56 (t, J=8 Hz, 1H), 6.58 (br s, 2H). cooled quenched with 2N hydrochloric acid (10 mL) The layers were separated the organic phase washed with 5% sodium hydroxide dried over magnesium sulfate concentrated The residue was refluxed in ethanol (12 mL) 6N hydrochloric acid (6 mL) overnight, then concentrated in vacuo The residue was dissolved in benzene (30 mL) treated with 5N ammonium hydroxide (20 mL) The organic extract was dried concentrated The crude product was purified by chromatography (silica gel, 0 to 5% ethyl acetate in hexane gradient elution)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-amino-3-chlorobenzophenone (0.730 g, 3.15 mmol) and ethyl glycinate hydrochloride salt (0.660 g, 4.72 mmol) in pyridine (15 mL) was refluxed using a Dean-Stark trap to remove water. After 30 h the reaction was cooled and concentrated. The residue was dissolve in methylene chloride and washed with saturated sodium bicarbonate. The crude product was purified by chromatography (silica gel, 0–30% ethyl acetate in hexane gradient elution) to give the title compound as a solid (0.557 g). 1H NMR (500 MHz, CDCl3) δ 7.83 (br s, 1H), 7.61 (dd, J=1, 8 Hz, 1H), 7.52 (m, 2H), 7.46 (tt, J=1,8 Hz, 1H), 7.39 (t, J=8 Hz, 2H), 7.26 (m, 1H), 7.11 (t, J=8 Hz, 1H), 4.36 (br s, 2H). to remove water After 30 h the reaction was cooled concentrated The residue was dissolve in methylene chloride washed with saturated sodium bicarbonate The crude product was purified by chromatography (silica gel, 0–30% ethyl acetate in hexane gradient elution)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Phenylmagnesium bromide (3.11 mL, 3.0 M in ether, 9.34 mmol) was added at room temperature to a solution of 8-chloro-2-methyl-4H-3,1-benzoxazin-4-one (2.15 g, 10.9 mmol) in benzene (10 mL) and tetrahydrofuran (3 mL). The reaction was refluxed for 2h, cooled, and quenched with 2N hydrochloric acid (10 mL). The layers were separated and the organic phase washed with 5% sodium hydroxide, dried over magnesium sulfate, and concentrated. The residue was refluxed in ethanol (12 mL) and 6N hydrochloric acid (6 mL) overnight, then concentrated in vacuo. The residue was dissolved in benzene (30 mL) and treated with 5N ammonium hydroxide (20 mL). The organic extract was dried and concentrated. The crude product was purified by chromatography (silica gel, 0 to 5% ethyl acetate in hexane gradient elution), giving the title compound (0.84 g). 1H NMR (500 MHz, CDCl3) δ 7.63 (d, J=7 Hz, 2H), 7.54 (t, J=7 Hz, 1H), 7.49–7.42 (m, 3H), 7.39 (d, J=8 Hz, 1H), 6.56 (t, J=8 Hz, 1H), 6.58 (br s, 2H). cooled quenched with 2N hydrochloric acid (10 mL) The layers were separated the organic phase washed with 5% sodium hydroxide dried over magnesium sulfate concentrated The residue was refluxed in ethanol (12 mL) 6N hydrochloric acid (6 mL) overnight, then concentrated in vacuo The residue was dissolved in benzene (30 mL) treated with 5N ammonium hydroxide (20 mL) The organic extract was dried concentrated The crude product was purified by chromatography (silica gel, 0 to 5% ethyl acetate in hexane gradient elution)