安非他酮杂质48

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: To a Grignard reactant prepared from 2.2 g. of magnesium turnings and 23.4 g. of 4-[2-(dimethylamino)-ethoxy]-bromobenzene in 100 ml. of dry tetrahydrofurane a solution of 10 g. of m-chloro-propiophenone in 30 ml. of tetrahydrofurane is added dropwise, at 20° C. The reaction mixture is stirred at room temperature for another two hours, cooled, and filtered onto a 20% aqueous ammonium chloride solution. Tetrahydrofurane is distilled off in vacuo. The residue is extracted with ether, the ethereal phase is washed with water, dried over anhydrous magnesium sulfate, filtered, and ether is distilled off. Crystallization of the residue from a mixture of n-hexane and ethyl acetate yields 14.2 g. of the named compound, melting at 108° to 109° C. cooled filtered onto a 20% aqueous ammonium chloride solution Tetrahydrofurane is distilled off in vacuo The residue is extracted with ether the ethereal phase is washed with water dried over anhydrous magnesium sulfate filtered ether is distilled off Crystallization of the residue from a mixture of n-hexane and ethyl acetate yields 14.2 g

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

实验步骤: A mixture of 75.0 g of m-chloropropiophenone and 200 ml of N,N-dimethylformamide dimethyl acetal was stirred and heated at reflux for 16 hours. The mixture was evaporated in vacuo to give a black oil. The oil was subjected to Kugelrohr distillation at 0.5 mm of mercury and the fraction that boils at 110° C. was removed. The residue from the distillation was collected to give 35.0 g of 3'-chloro-3-dimethylamino-2-methylacrylophenone as a black oil. heated at reflux for 16 hours The mixture was evaporated in vacuo to give a black oil The oil was subjected to Kugelrohr distillation at 0.5 mm of mercury the fraction that boils at 110° C. was removed The residue from the distillation was collected

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

实验步骤: The racemate of the morpholinol metabolite of bupropion hydrochloride ((+/−)-(2R*,3R*)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol hydrochloride) may be synthesized by the following process. To 3′-chloropropiophenone (10.0 g, 0.06 mol) in dioxane (50 mL) was added a solution of dioxane dibromide (14.9 g, 0.06 mol) in dioxane (50 mL). The reaction mixture was stirred for 2 h at ambient temperature and poured into a mixture of ice and water (500 mL). The mixture was extracted several times with methylene chloride. The combined extracts were dried (Na2SO4) and concentrated in vacuo to give 14.8 g (85%) of 2-bromo-3′-chloropropiophenone as a pale yellow oil. This was used without further purification. NMR (300 Mhz, CDCl3); δ 7.99 (m, 1H), 7.90 (d, 1H), 7.57 (d, 1H), 7.44 (t, 1H), 5.22 (q, 1H), 1.91 (t, 3H). The mixture was extracted several times with methylene chloride The combined extracts were dried (Na2SO4) concentrated in vacuo

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

实验步骤: The racemate of the morpholinol metabolite of bupropion hydrochloride ((+/−)-(2R*,3R*)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol hydrochloride) may be synthesized by the following process. To 3′-chloropropiophenone (10.0 g, 0.06 mol) in dioxane (50 mL) was added a solution of dioxane dibromide (14.9 g, 0.06 mol) in dioxane (50 mL). The reaction mixture was stirred for 2 h at ambient temperature and poured into a mixture of ice and water (500 mL). The mixture was extracted several times with methylene chloride. The combined extracts were dried (Na2SO4) and concentrated in vacuo to give 14.8 g (85%) of 2-bromo-3′-chloropropiophenone as a pale yellow oil. This was used without further purification. NMR (300 Mhz, CDCl3); δ 7.99 (m, 1H), 7.90 (d, 1H), 7.57 (d, 1H), 7.44 (t, 1H), 5.22 (q, 1H), 1.91 (t, 3H). The mixture was extracted several times with methylene chloride The combined extracts were dried (Na2SO4) concentrated in vacuo

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

实验步骤: The racemate of the morpholinol metabolite of bupropion hydrochloride ((+/−)-(2R*,3R*)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol hydrochloride) may be synthesized by the following process. To 3′-chloropropiophenone (10.0 g, 0.06 mol) in dioxane (50 mL) was added a solution of dioxane dibromide (14.9 g, 0.06 mol) in dioxane (50 mL). The reaction mixture was stirred for 2h at ambient temperature and poured into a mixture of ice and water (500 mL). The mixture was extracted several times with methylene chloride. The combined extracts were dried (Na2SO4) and concentrated in vacuo to give 14.8 g (85%) of 2-bromo-3′-chloropropiophenone as a pale yellow oil. This was used without further purification. NMR (300 Mhz, CDCl3); δ 7.99 (m, 1H), 7.90 (d, 1H), 7.57 (d, 1H), 7.44 (t, 1H), 5.22 (q, 1H), 1.91 (t, 3H). The mixture was extracted several times with methylene chloride The combined extracts were dried (Na2SO4) concentrated in vacuo

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

实验步骤: To a Grignard reactant prepared from 2.2 g. of magnesium turnings and 23.4 g. of 4-[2-(dimethylamino)-ethoxy]-bromobenzene in 100 ml. of dry tetrahydrofurane a solution of 10 g. of m-chloro-propiophenone in 30 ml. of tetrahydrofurane is added dropwise, at 20° C. The reaction mixture is stirred at room temperature for another two hours, cooled, and filtered onto a 20% aqueous ammonium chloride solution. Tetrahydrofurane is distilled off in vacuo. The residue is extracted with ether, the ethereal phase is washed with water, dried over anhydrous magnesium sulfate, filtered, and ether is distilled off. Crystallization of the residue from a mixture of n-hexane and ethyl acetate yields 14.2 g. of the named compound, melting at 108° to 109° C. cooled filtered onto a 20% aqueous ammonium chloride solution Tetrahydrofurane is distilled off in vacuo The residue is extracted with ether the ethereal phase is washed with water dried over anhydrous magnesium sulfate filtered ether is distilled off Crystallization of the residue from a mixture of n-hexane and ethyl acetate yields 14.2 g

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

实验步骤: A mixture of 75.0 g of m-chloropropiophenone and 200 ml of N,N-dimethylformamide dimethyl acetal was stirred and heated at reflux for 16 hours. The mixture was evaporated in vacuo to give a black oil. The oil was subjected to Kugelrohr distillation at 0.5 mm of mercury and the fraction that boils at 110° C. was removed. The residue from the distillation was collected to give 35.0 g of 3'-chloro-3-dimethylamino-2-methylacrylophenone as a black oil. heated at reflux for 16 hours The mixture was evaporated in vacuo to give a black oil The oil was subjected to Kugelrohr distillation at 0.5 mm of mercury the fraction that boils at 110° C. was removed The residue from the distillation was collected

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

实验步骤: The racemate of the morpholinol metabolite of bupropion hydrochloride ((+/−)-(2R*,3R*)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol hydrochloride) may be synthesized by the following process. To 3′-chloropropiophenone (10.0 g, 0.06 mol) in dioxane (50 mL) was added a solution of dioxane dibromide (14.9 g, 0.06 mol) in dioxane (50 mL). The reaction mixture was stirred for 2 h at ambient temperature and poured into a mixture of ice and water (500 mL). The mixture was extracted several times with methylene chloride. The combined extracts were dried (Na2SO4) and concentrated in vacuo to give 14.8 g (85%) of 2-bromo-3′-chloropropiophenone as a pale yellow oil. This was used without further purification. NMR (300 Mhz, CDCl3); δ 7.99 (m, 1H), 7.90 (d, 1H), 7.57 (d, 1H), 7.44 (t, 1H), 5.22 (q, 1H), 1.91 (t, 3H). The mixture was extracted several times with methylene chloride The combined extracts were dried (Na2SO4) concentrated in vacuo

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

实验步骤: To 1 mole of m-chloropropiophenone heated to 85±5° C., bromine was added dropwise under stirring. The reaction temperature was kept at 85±5° C. during and after the addition of bromine, and the reaction was carried on for 2 hours. Then m-chloro-α-bromopropiophenone (compound of formula (II)) was obtained. was kept at 85±5° C. was carried on for 2 hours

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

实验步骤: To 1 mole of m-chloropropiophenone was heated to 70±5° C., bromine was added dropwise under stirring. The reaction temperature was kept at 70±5° C. during the addition of bromine and kept for 5.5 hours after the addition. m-chloro-α-bromopropiophenone (compound of formula (II)) was obtained. after the addition

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

实验步骤: To 1 mole of m-chloropropiophenone heated to 60±5° C., bromine was added dropwise under stirring. The reaction temperature was kept at 60±5° C. during the addition of bromine, and kept for 5.5 hours after the addition. m-Chloro-α-bromopropiophenone (compound of formula (II)) was obtained. after the addition