(<I>R</I>)-(-)-3-奎宁醇 盐酸盐

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

实验步骤: (R)-3-Quinuclidinol hydrochloride (Aldrich, 20 g, 12.2 mmol) was treated with NaOH aqueous solution (20%, 50 mL) at ambient temperature for 10 minutes and extracted with CHCO3/isopropyl alcohol (10:1, 3×200 mL). The extracts were combine, washed with brine (50 mL), dried over MgSO4, filtered, and the filtrate was concentrated under reduced pressure to give the title compound as a white solid (15. 5 g, yield, 99%). 1H NMR (300 MHz, MeOH-d4) δ 1.36-1.50 (m, 1H), 1.52-1.60 (m, 1H), 1.76-1.85 (m, 2H), 1.90-2.05 (m, 1H), 2.50-2.95 (m, 5H), 3.10 (ddd, J=14.2, 8.4, 2.3 Hz, 1H), 3.82-3.88 (m, 1H) ppm. MS (DCl/NH3): m/z 128 (M+H)+. extracted with CHCO3/isopropyl alcohol (10:1, 3×200 mL) washed with brine (50 mL) dried over MgSO4 filtered the filtrate was concentrated under reduced pressure

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

实验步骤: (R)-3-Quinuclidinol hydrochloride (20 g, 12.2 mmol; Aldrich) was treated with aq. NaOH (20%, 50 mL) at ambient temperature for 10 min, then extracted with CHCl3/i-PrOH (10:1, 3×200 mL). The extracts were combined, washed with brine (50 mL) and dried over MgSO4. After removal of the drying agents by filtration, the filtrate was concentrated under reduced pressure to afford the title compound as white solid (15.5 g, 122 mmol, 99% yield). 1H NMR (300 MHz, methanol-d4) δ 3.88-3.82 (1H, m), 3.10 (1H, ddd, J=14, 8, 2 Hz), 2.95-2.50 (5H, m), 2.05-1.90 (1H, m), 1.85-1.76 (2H, m), 1.60-1.52 (1H, m), 1.50-1.36 (1H, m). MS (DCl/NH3): m/z 128 (M+1)+. extracted with CHCl3/i-PrOH (10:1, 3×200 mL) washed with brine (50 mL) dried over MgSO4 After removal of the drying agents by filtration the filtrate was concentrated under reduced pressure

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

实验步骤: 2-Biphenyl isocyanate (1.00 g, 5.12 mmol) and (R)-(−)-3-quinuclidinol hydrochloride (921 mg, 5.63 mmol) were heated together in N,N-dimethylformamide (2.06 mL) at 110° C. for 12 h. The reaction mixture was cooled and diluted with ethyl acetate (15 mL) and then washed with saturated aqueous sodium bicarbonate (2×10 mL). The organic layer was extracted with 1 M hydrochloric acid (3×20 mL) and the combined aqueous extracts were made basic to pH 8-9 with potassium carbonate. The aqueous layer was then extracted with ethyl acetate (3×20 mL) and the combined organic layers were dried (magnesium sulfate) and solvent was removed under reduced pressure to give the title compound as a yellow oil (1.64 g, 99% yield). The reaction mixture was cooled washed with saturated aqueous sodium bicarbonate (2×10 mL) The organic layer was extracted with 1 M hydrochloric acid (3×20 mL) The aqueous layer was then extracted with ethyl acetate (3×20 mL) the combined organic layers were dried (magnesium sulfate) and solvent was removed under reduced pressure

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

实验步骤: 2-Biphenyl isocyanate (1.00 g, 5.12 mmol) and (R)-(−)-3-quinuclidinol hydrochloride (921 mg, 5.63 mmol) were heated together in N,N-dimethylformamide (2.06 mL) at 110° C. for 12 h. The reaction mixture was cooled and diluted with ethyl acetate (15 mL) and then washed with saturated aqueous sodium bicarbonate (2×10 mL). The organic layer was extracted with 1 M hydrochloric acid (3×20 mL) and the combined aqueous extracts were made basic to pH 8-9 with potassium carbonate. The aqueous layer was then extracted with ethyl acetate (3×20 mL) and the combined organic layers were dried (magnesium sulfate) and solvent was removed under reduced pressure to give the title compound as a yellow oil (1.64 g, 99% yield). The reaction mixture was cooled washed with saturated aqueous sodium bicarbonate (2×10 mL) The organic layer was extracted with 1 M hydrochloric acid (3×20 mL) The aqueous layer was then extracted with ethyl acetate (3×20 mL) the combined organic layers were dried (magnesium sulfate) and solvent was removed under reduced pressure

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

实验步骤: 2-Biphenyl isocyanate (1.00 g, 5.12 mmol) and (R)-(−)-3-quinuclidinol hydrochloride (921 mg, 5.63 mmol) were heated together in N,N-dimethylformamide (2.06 mL) at 110° C. for 12 h. The reaction mixture was cooled and diluted with ethyl acetate (15 mL) and then washed with saturated aqueous sodium bicarbonate (2×10 mL). The organic layer was extracted with 1 M hydrochloric acid (3×20 mL) and the combined aqueous extracts were made basic to pH 8-9 with potassium carbonate. The aqueous layer was then extracted with ethyl acetate (3×20 mL) and the combined organic layers were dried (magnesium sulfate) and solvent was removed under reduced pressure to give the title compound as a yellow oil (1.64 g, 99% yield). The reaction mixture was cooled washed with saturated aqueous sodium bicarbonate (2×10 mL) The organic layer was extracted with 1 M hydrochloric acid (3×20 mL) The aqueous layer was then extracted with ethyl acetate (3×20 mL) the combined organic layers were dried (magnesium sulfate) and solvent was removed under reduced pressure

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

实验步骤: 2-Biphenyl isocyanate (1.00 g, 5.12 mmol) and (R)-(−)-3-quinuclidinol hydrochloride (921 mg, 5.63 mmol) were heated together in N,N-dimethylformamide (2.06 mL) at 110° C. for 12 h. The reaction mixture was cooled and diluted with ethyl acetate (15 mL) and then washed with saturated aqueous sodium bicarbonate (2×10 mL). The organic layer was extracted with 1 M hydrochloric acid (3×20 mL) and the combined aqueous extracts were made basic to pH 8-9 with potassium carbonate. The aqueous layer was then extracted with ethyl acetate (3×20 mL) and the combined organic layers were dried (magnesium sulfate) and solvent was removed under reduced pressure to give the title compound as a yellow oil (1.64 g, 99% yield). The reaction mixture was cooled washed with saturated aqueous sodium bicarbonate (2×10 mL) The organic layer was extracted with 1 M hydrochloric acid (3×20 mL) The aqueous layer was then extracted with ethyl acetate (3×20 mL) the combined organic layers were dried (magnesium sulfate) and solvent was removed under reduced pressure

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

实验步骤: 2-Biphenyl isocyanate (1.00 g, 5.12 mmol) and (R)-(−)-3-quinuclidinol hydrochloride (921 mg, 5.63 mmol) were heated together in N,N-dimethylformamide (2.06 mL) at 110° C. for 12 h. The reaction mixture was cooled and diluted with ethyl acetate (15 mL) and then washed with saturated aqueous sodium bicarbonate (2×10 mL). The organic layer was extracted with 1 M hydrochloric acid (3×20 mL) and the combined aqueous extracts were made basic to pH 8-9 with potassium carbonate. The aqueous layer was then extracted with ethyl acetate (3×20 mL) and the combined organic layers were dried (magnesium sulfate) and solvent was removed under reduced pressure to give the title compound as a yellow oil (1.64 g, 99% yield). The reaction mixture was cooled washed with saturated aqueous sodium bicarbonate (2×10 mL) The organic layer was extracted with 1 M hydrochloric acid (3×20 mL) The aqueous layer was then extracted with ethyl acetate (3×20 mL) the combined organic layers were dried (magnesium sulfate) and solvent was removed under reduced pressure

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

实验步骤: 2-Biphenyl isocyanate (1.00 g, 5.12 mmol) and (R)-(−)-3-quinuclidinol hydrochloride (921 mg, 5.63 mmol) were heated together in N,N-dimethylformamide (2.06 mL) at 110° C. for 12 h. The reaction mixture was cooled and diluted with ethyl acetate (15 mL) and then washed with saturated aqueous sodium bicarbonate (2×10 mL). The organic layer was extracted with 1 M hydrochloric acid (3×20 mL) and the combined aqueous extracts were made basic to pH 8–9 with potassium carbonate. The aqueous layer was then extracted with ethyl acetate (3×20 mL) and the combined organic layers were dried (magnesium sulfate) and solvent was removed under reduced pressure to give the title compound as a yellow oil (1.64 g, 99% yield). The reaction mixture was cooled washed with saturated aqueous sodium bicarbonate (2×10 mL) The organic layer was extracted with 1 M hydrochloric acid (3×20 mL) The aqueous layer was then extracted with ethyl acetate (3×20 mL) the combined organic layers were dried (magnesium sulfate) and solvent was removed under reduced pressure

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

实验步骤: 2-Biphenyl isocyanate (1.00 g, 5.12 mmol) and (R)-(−)-3-quinuclidinol hydrochloride (921 mg, 5.63 mmol) were heated together in N,N-dimethylformamide (2.06 mL) at 110° C. for 12 h. The reaction mixture was cooled and diluted with ethyl acetate (15 mL) and then washed with saturated aqueous sodium bicarbonate (2×10 mL). The organic layer was extracted with 1 M hydrochloric acid (3×20 mL) and the combined aqueous extracts were made basic to pH 8–9 with potassium carbonate. The aqueous layer was then extracted with ethyl acetate (3×20 mL) and the combined organic layers were dried (magnesium sulfate) and solvent was removed under reduced pressure to give the title compound as a yellow oil (1.64 g, 99% yield). The reaction mixture was cooled washed with saturated aqueous sodium bicarbonate (2×10 mL) The organic layer was extracted with 1 M hydrochloric acid (3×20 mL) The aqueous layer was then extracted with ethyl acetate (3×20 mL) the combined organic layers were dried (magnesium sulfate) and solvent was removed under reduced pressure

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

实验步骤: (R)-3-Quinuclidinol hydrochloride (20 g, 12.2 mmol; Aldrich) was treated with aq. NaOH (20%, 50 mL) at ambient temperature for 10 min, then extracted with CHCl3/iPrOH (10:1, 3×200 mL). The extracts were combined, washed with brine (50 mL) and dried over MgSO4. After removal of the drying agents by filtration, the filtrate was concentrated under reduced pressure to afford the title compound as white solid (15.5 g, 122 mmol, 99% yield). 1H NMR (300 MHz, methanol-d4) δ 3.88-3.82 (1H, m), 3.10 (1H, ddd, J=14, 8, 2 Hz), 2.95-2.50 (5H, m), 2.05-1.90 (1H, m), 1.85-1.76 (2H, m), 1.60-1.52 (1H, m), 1.50-1.36 (1H, m). MS (DCI/NH3): m/z 128 (M+1)+. extracted with CHCl3/iPrOH (10:1, 3×200 mL) washed with brine (50 mL) dried over MgSO4 After removal of the drying agents by filtration the filtrate was concentrated under reduced pressure

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

实验步骤: (3R)-3-Quinuclidinol hydrochloride (Aldrich, 20 g, 12.2 mmol) was treated with NaOH aqueous solution(20%, 50 mL) at ambient temperature for 10 min. It was then extracted with CHCl3/iPrOH (v.10: 1, 3×200 mL). The extracts were combine, washed with brine (50 mL) and dried over MgSO4. The drying agents were removed by filtration and the filtrates was concentrated under reduced pressure to give the title compound as white solid (15. 5 g, yield, 99%). 1H NMR (300 MHz, CD3OD) δ 1.36-1.50 (m, 1H), 1.52-1.60 (m, 1H), 1.76-1.85 (m, 2H), 1.90-2.05 (m, 1H), 2.50-2.95(m, 5H), 3.10 (ddd, J=14.2, 8.4, 2.3 Hz, 1H), 3.82-3.88 (m, 1H) ppm. MS (DCI/NH3): m/z 128 (M+H)+. It was then extracted with CHCl3/iPrOH (v.10: 1, 3×200 mL) washed with brine (50 mL) dried over MgSO4 The drying agents were removed by filtration the filtrates was concentrated under reduced pressure

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

实验步骤: 2-Biphenyl isocyanate (1.00 g, 5.12 mmol) and (R)-(−)-3-quinuclidinol hydrochloride (921 mg, 5.63 mmol) were heated together in N,N-dimethylformamide (2.06 mL) at 110° C. for 12 h. The reaction mixture was cooled and diluted with ethyl acetate (15 mL) and then washed with saturated aqueous sodium bicarbonate (2×10 mL). The organic layer was extracted with 1 M hydrochloric acid (3×20 mL) and the combined aqueous extracts were made basic to pH 8-9 with potassium carbonate. The aqueous layer was then extracted with ethyl acetate (3×20 mL) and the combined organic layers were dried (magnesium sulfate) and solvent was removed under reduced pressure to give the title compound as a yellow oil (1.64 g, 99% yield). The reaction mixture was cooled washed with saturated aqueous sodium bicarbonate (2×10 mL) The organic layer was extracted with 1 M hydrochloric acid (3×20 mL) The aqueous layer was then extracted with ethyl acetate (3×20 mL) the combined organic layers were dried (magnesium sulfate) and solvent was removed under reduced pressure