(1S)-1-amino-2-methyl-1-phenylpropan-2-ol

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of C2 (38.8 g, 235 mmol) in dichloromethane (1000 mL) was treated with carbonyldiimidazole (45.6 g, 281 mmol) and heated at reflux for 2 hours. The reaction mixture was cooled to 25° C., quenched with 1 N hydrochloric acid (560 mL), and extracted with dichloromethane (3×). The combined organic extracts were dried over sodium sulfate and concentrated, and the resultant residue was purified by trituration with 4:1 hexanes: ethyl acetate, followed by chromatography on silica gel (gradient: 9:1 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate) to provide C3 as a white solid. Yield: 24.7 g, 55%. MS (APCI) m/z 192.2 (M+1). 1H NMR (400 MHz, CDCl3) δ 0.91 (3H, s), 1.58 (3H, s), 4.62 (1H, s), 5.53-5.60 (1H, br s), 7.20-7.39 (5H, m). heated at reflux for 2 hours quenched with 1 N hydrochloric acid (560 mL) extracted with dichloromethane (3×) The combined organic extracts were dried over sodium sulfate concentrated the resultant residue was purified by trituration with 4:1 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 (S)-1-amino-2-methyl-1-phenylpropan-2-ol (2.0 g, 10 mmol) in H2O (10 mL) was added potassium cyanate (0.85 g, 12 mmol) and the contents were stirred at ambient temperature for 2 h. The solid thus obtained was filtered and washed successively with H2O (2×5 mL) and dried in air to afford (S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)urea. 1H NMR (400 MHz, DMSO-d6) δ 7.25-7.15 (m, 5H), 6.52 (d, J=9.2 Hz, 1H), 5.50 (s, 2H), 4.50 (s, 1H), 4.41 (d, J=9.2 Hz, 1H), 1.10 (s, 3H), 0.93 (s, 3H). Anal. Calcd. C11H16N2O2 208.3. Found 209.2 (M+H). The solid thus obtained was filtered washed successively with H2O (2×5 mL) dried in air

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

実験手順: To a solution of (S)-tert-butyl(2-hydroxy-2-methyl-1-phenylpropyl)carbamate (3.5 g, 13 mmol) in CH2Cl2 (20 mL) was added dioxane saturated with HCl gas (10 mL) and the contents were stirred at ambient temperature for 30 min. The volatiles were then removed under reduced pressure and the residue thus obtained was triturated with Et2O to afford (S)-1-amino-2-methyl-1-phenylpropan-2-ol. 1H NMR (300 MHz, DMSO-d6) δ 8.3 (bs, 2H), 7.47-7.37 (m, 5H), 5.34 (s, 1H), 4.1 (bs, 1H), 1.17 (s, 3H), 0.97 (s, 3H). Anal. Calcd. C10H15NO 165.2. Found 166.2 (M+H). The volatiles were then removed under reduced pressure the residue thus obtained was triturated with Et2O

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

実験手順: To a solution of (S)-tert-butyl(2-hydroxy-2-methyl-1-phenylpropyl)carbamate (3.5 g, 13 mmol) in CH2Cl2 (20 mL) was added dioxane saturated with HCl gas (10 mL) and the contents were stirred at ambient temperature for 30 min. The volatiles were then removed under reduced pressure and the residue thus obtained was triturated with Et2O to afford (S)-1-amino-2-methyl-1-phenylpropan-2-ol. 1H NMR (300 MHz, DMSO-d6) δ 8.3 (bs, 2H), 7.47-7.37 (m, 5H), 5.34 (s, 1H), 4.1 (bs, 1H), 1.17 (s, 3H), 0.97 (s, 3H). Anal. Calcd. C10H15NO 165.2. Found 166.2 (M+H). The volatiles were then removed under reduced pressure the residue thus obtained was triturated with Et2O

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

実験手順: To a flask charged with boc-4-piperidone (2.412 g, 12.10 mmol, Alfa-Aesar) was added DCM (60.5 mL), acetic acid (0.901 mL, 15.74 mmol), (S)-1-amino-2-methyl-1-phenylpropan-2-ol (2 g, 12.10 mmol, BOC Scientific) and sodium triacetoxyborohydride (3.59 g, 16.95 mmol) respectively. The resulting orange suspension was stirred at room temperature for 3 h. LCMS indicated good conversion to desired product. To the mixture was added saturated NaHCO3 and K2CO3 pellets. The mixture was transferred to a separatory funnel and extracted with DCM (2×). The combined organics were dried with Na2SO4, filtered, and dried under reduced pressure. The material thus obtained was used without further purification.

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

実験手順: To a flask charged with boc-4-piperidone (2.412 g, 12.10 mmol, Alfa-Aesar) was added DCM (60.5 mL), acetic acid (0.901 mL, 15.74 mmol), (S)-1-amino-2-methyl-1-phenylpropan-2-ol (2 g, 12.10 mmol, BOC Scientific) and sodium triacetoxyborohydride (3.59 g, 16.95 mmol) respectively. The resulting orange suspension was stirred at room temperature for 3 h. LCMS indicated good conversion to desired product. To the mixture was added saturated NaHCO3 and K2CO3 pellets. The mixture was transferred to a separatory funnel and extracted with DCM (2×). The combined organics were dried with Na2SO4, filtered, and dried under reduced pressure. The material thus obtained was used without further purification.

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of C2 (38.8 g, 235 mmol) in dichloromethane (1000 mL) was treated with carbonyldiimidazole (45.6 g, 281 mmol) and heated at reflux for 2 hours. The reaction mixture was cooled to 25° C., quenched with 1 N hydrochloric acid (560 mL), and extracted with dichloromethane (3×). The combined organic extracts were dried over sodium sulfate and concentrated, and the resultant residue was purified by trituration with 4:1 hexanes:ethyl acetate, followed by chromatography on silica gel (gradient: 9:1 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate) to provide C3 as a white solid. Yield: 24.7 g, 55%. MS (APCI) m/z 192.2 (M+1). 1H NMR (400 MHz, CDCl3) δ 0.91 (3H, s), 1.58 (3H, s), 4.62 (1H, s), 5.53-5.60 (1H, br s), 7.20-7.39 (5H, m). heated at reflux for 2 hours quenched with 1 N hydrochloric acid (560 mL) extracted with dichloromethane (3×) The combined organic extracts were dried over sodium sulfate concentrated the resultant residue was purified by trituration with 4:1 hexanes

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of C2 (38.8 g, 235 mmol) in dichloromethane (1000 mL) was treated with carbonyldiimidazole (45.6 g, 281 mmol) and heated at reflux for 2 hours. The reaction mixture was cooled to 25° C., quenched with 1 N hydrochloric acid (560 mL), and extracted with dichloromethane (3×). The combined organic extracts were dried over sodium sulfate and concentrated, and the resultant residue was purified by trituration with 4:1 hexanes:ethyl acetate, followed by chromatography on silica gel (gradient: 9:1 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate) to provide C3 as a white solid. Yield: 24.7 g, 55%. MS (APCI) m/z 192.2 (M+1). 1H NMR (400 MHz, CDCl3) δ 0.91 (3H, s), 1.58 (3H, s), 4.62 (1H, s), 5.53-5.60 (1H, br s), 7.20-7.39 (5H, m). heated at reflux for 2 hours quenched with 1 N hydrochloric acid (560 mL) extracted with dichloromethane (3×) The combined organic extracts were dried over sodium sulfate concentrated the resultant residue was purified by trituration with 4:1 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 (S)-1-amino-2-methyl-1-phenylpropan-2-ol (2.0 g, 10 mmol) in H2O (10 mL) was added potassium cyanate (0.85 g, 12 mmol) and the contents were stirred at ambient temperature for 2 h. The solid thus obtained was filtered and washed successively with H2O (2×5 mL) and dried in air to afford (S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)urea. 1H NMR (400 MHz, DMSO-d6) δ 7.25-7.15 (m, 5H), 6.52 (d, J=9.2 Hz, 1H), 5.50 (s, 2H), 4.50 (s, 1H), 4.41 (d, J=9.2 Hz, 1H), 1.10 (s, 3H), 0.93 (s, 3H). Anal. Calcd. C11H16N2O2 208.3. Found 209.2 (M+H). The solid thus obtained was filtered washed successively with H2O (2×5 mL) dried in air

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

実験手順: To a solution of (S)-tert-butyl(2-hydroxy-2-methyl-1-phenylpropyl)carbamate (3.5 g, 13 mmol) in CH2Cl2 (20 mL) was added dioxane saturated with HCl gas (10 mL) and the contents were stirred at ambient temperature for 30 min. The volatiles were then removed under reduced pressure and the residue thus obtained was triturated with Et2O to afford (S)-1-amino-2-methyl-1-phenylpropan-2-ol. 1H NMR (300 MHz, DMSO-d6) δ 8.3 (bs, 2H), 7.47-7.37 (m, 5H), 5.34 (s, 1H), 4.1 (bs, 1H), 1.17 (s, 3H), 0.97 (s, 3H). Anal. Calcd. C10H15NO 165.2. Found 166.2 (M+H). The volatiles were then removed under reduced pressure the residue thus obtained was triturated with Et2O

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

実験手順: To a flask charged with boc-4-piperidone (2.412 g, 12.10 mmol, Alfa-Aesar) was added DCM (60.5 mL), acetic acid (0.901 mL, 15.74 mmol), (S)-1-amino-2-methyl-1-phenylpropan-2-ol (2 g, 12.10 mmol, BOC Scientific) and sodium triacetoxyborohydride (3.59 g, 16.95 mmol) respectively. The resulting orange suspension was stirred at room temperature for 3 h. LCMS indicated good conversion to desired product. To the mixture was added saturated NaHCO3 and K2CO3 pellets. The mixture was transferred to a separatory funnel and extracted with DCM (2×). The combined organics were dried with Na2SO4, filtered, and dried under reduced pressure. The material thus obtained was used without further purification.

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of C2 (38.8 g, 235 mmol) in dichloromethane (1000 mL) was treated with carbonyldiimidazole (45.6 g, 281 mmol) and heated at reflux for 2 hours. The reaction mixture was cooled to 25° C., quenched with 1 N hydrochloric acid (560 mL), and extracted with dichloromethane (3×). The combined organic extracts were dried over sodium sulfate and concentrated, and the resultant residue was purified by trituration with 4:1 hexanes: ethyl acetate, followed by chromatography on silica gel (gradient: 9:1 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate) to provide C3 as a white solid. Yield: 24.7 g, 55%. MS (APCI) m/z 192.2 (M+1). 1H NMR (400 MHz, CDCl3) δ 0.91 (3H, s), 1.58 (3H, s), 4.62 (1H, s), 5.53-5.60 (1H, br s), 7.20-7.39 (5H, m). heated at reflux for 2 hours quenched with 1 N hydrochloric acid (560 mL) extracted with dichloromethane (3×) The combined organic extracts were dried over sodium sulfate concentrated the resultant residue was purified by trituration with 4:1 hexanes