1-bromo-7-methyloctane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of (S)-nicotine (0.37 g, 2.3 mmol) in AcOH (10 ml) was added 1-bromo-7-methyl-octane (1.20 g, 5.80 mmol). The mixture was heated at reflux for 3 days. AcOH was evaporated and the residue was recrystallized in ethyl acetate-CHCl3 to (S)-1-(7-methyl-octyl)-3-(1-methyl-pyrrolidin-2-yl)-pyridinium bromide hydrobromide salt (NONB-7M) (0.60 g, 58%) as hygroscopic white crystals: 1H NMR (300 MHz, CDCl3) δ 11.85 (1H, s), 10.61 (1H, s), 9.68 (1H, d, J=8.4 Hz), 8.83 (1H, d, J=6.0 Hz), 8.24 (1H, dd, J=8.1, 6.3 Hz), 5.80 (1H, m), 4.75 (2H, m), 4.01 (1H, m), 3.32 (1H, m), 2.96 (3H, d, J=4.8 Hz), 2.74 (1H, m), 2.30–2.60 (3H, m), 2.11 (2H, m), 1.05–1.55 (9H, m), 0.82 (6H, d, J=6.6 Hz); 13C NMR (75 MHz, CDCl3) δ 147.64, 146.61, 144.97, 134.71, 129.09, 67.21, 63.13, 56.16, 38.97, 32.15, 31.82, 29.48, 28.10, 27.36, 26.55, 22.86, 21.97; Anal. Calcd for C19H34Br2N2.0.3H2O: C, 50.09; H, 7.63; N, 6.15. Found: C, 50.08; H, 7.64; N, 6.13. The mixture was heated at reflux for 3 days AcOH was evaporated the residue was recrystallized in ethyl acetate-CHCl3 to (S)-1-(7-methyl-octyl)-3-(1-methyl-pyrrolidin-2-yl)-pyridinium bromide hydrobromide salt (NONB-7M) (0.60 g, 58%) as hygroscopic white crystals

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 7-methyl-octan-1-ol (1.20 g, 8.33 mmol) in DMF (20 mL) was added triphenylphosphine (2.43 g, 9.26 mmol). The solution was cooled to 0° C. and NBS (1.60 g, 8.99 mmol) was added in portions. After stirring for 30 min at room temperature, the reaction was quenched with methanol (1 mL). The solution was diluted with ether (100 mL), washed with water, saturated aqueous NaHCO3 and brine successively. The organic layer was dried and concentrated. The residue was purified by flash chromatography on silica gel, eluting with hexane to afford 1-bromo-7-methyl-octane (1.28 g, 74%) as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 3.41 (2H, t, J=6.6 Hz), 1.85 (2H, m), 1.52 (1H, m), 1.42 (2H, m), 1.28 (4H, m), 1.17 (2H, m), 0.87 (3H, s), 0.85 (3H, s); 13C NMR (75 MHz, CDCl3) δ 39.16, 34.34, 33.14, 29.34, 28.52, 28.24, 27.51, 22.94. the reaction was quenched with methanol (1 mL) The solution was diluted with ether (100 mL) washed with water, saturated aqueous NaHCO3 and brine successively The organic layer was dried concentrated The residue was purified by flash chromatography on silica gel eluting with hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of (S)-nicotine (0.37 g, 2.3 mmol) in AcOH (10 ml) was added 1-bromo-7-methyl-octane (1.20 g, 5.80 mmol). The mixture was heated at reflux for 3 days. AcOH was evaporated and the residue was recrystallized in ethyl acetate-CHCl3 to (S)-1-(7-methyl-octyl)-3-(1-methyl-pyrrolidin-2-yl)-pyridinium bromide hydrobromide salt (NONB-7M) (0.60 g, 58%) as hygroscopic white crystals: 1H NMR (300 MHz, CDCl3) δ 11.85 (1H, s), 10.61 (1H, s), 9.68 (1H, d, J=8.4 Hz), 8.83 (1H, d, J=6.0 Hz), 8.24 (1H, dd, J=8.1, 6.3 Hz), 5.80 (1H, m), 4.75 (2H, m), 4.01 (1H, m), 3.32 (1H, m), 2.96 (3H, d, J=4.8 Hz), 2.74 (1H, m), 2.30–2.60 (3H, m), 2.11 (2H, m), 1.05–1.55 (9H, m), 0.82 (6H, d, J=6.6 Hz); 13C NMR (75 MHz, CDCl3) δ 147.64, 146.61, 144.97, 134.71, 129.09, 67.21, 63.13, 56.16, 38.97, 32.15, 31.82, 29.48, 28.10, 27.36, 26.55, 22.86, 21.97; Anal. Calcd for C19H34Br2N2.0.3H2O: C, 50.09; H, 7.63; N, 6.15. Found: C, 50.08; H, 7.64; N, 6.13. The mixture was heated at reflux for 3 days AcOH was evaporated the residue was recrystallized in ethyl acetate-CHCl3 to (S)-1-(7-methyl-octyl)-3-(1-methyl-pyrrolidin-2-yl)-pyridinium bromide hydrobromide salt (NONB-7M) (0.60 g, 58%) as hygroscopic white crystals

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 7-methyl-octan-1-ol (1.20 g, 8.33 mmol) in DMF (20 mL) was added triphenylphosphine (2.43 g, 9.26 mmol). The solution was cooled to 0° C. and NBS (1.60 g, 8.99 mmol) was added in portions. After stirring for 30 min at room temperature, the reaction was quenched with methanol (1 mL). The solution was diluted with ether (100 mL), washed with water, saturated aqueous NaHCO3 and brine successively. The organic layer was dried and concentrated. The residue was purified by flash chromatography on silica gel, eluting with hexane to afford 1-bromo-7-methyl-octane (1.28 g, 74%) as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 3.41 (2H, t, J=6.6 Hz), 1.85 (2H, m), 1.52 (1H, m), 1.42 (2H, m), 1.28 (4H, m), 1.17 (2H, m), 0.87 (3H, s), 0.85 (3H, s); 13C NMR (75 MHz, CDCl3) δ 39.16, 34.34, 33.14, 29.34, 28.52, 28.24, 27.51, 22.94. the reaction was quenched with methanol (1 mL) The solution was diluted with ether (100 mL) washed with water, saturated aqueous NaHCO3 and brine successively The organic layer was dried concentrated The residue was purified by flash chromatography on silica gel eluting with hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of (S)-nicotine (0.37 g, 2.3 mmol) in AcOH (10 ml) was added 1-bromo-7-methyl-octane (1.20 g, 5.80 mmol). The mixture was heated at reflux for 3 days. AcOH was evaporated and the residue was recrystallized in ethyl acetate-CHCl3 to (S)-1-(7-methyl-octyl)-3-(1-methyl-pyrrolidin-2-yl)-pyridinium bromide hydrobromide salt (NONB-7M) (0.60 g, 58%) as hygroscopic white crystals: 1H NMR (300 MHz, CDCl3) δ 11.85 (1H, s), 10.61 (1H, s), 9.68 (1H, d, J=8.4 Hz), 8.83 (1H, d, J=6.0 Hz), 8.24 (1H, dd, J=8.1, 6.3 Hz), 5.80 (1H, m), 4.75 (2H, m), 4.01 (1H, m), 3.32 (1H, m), 2.96 (3H, d, J=4.8 Hz), 2.74 (1H, m), 2.30–2.60 (3H, m), 2.11 (2H, m), 1.05–1.55 (9H, m), 0.82 (6H, d, J=6.6 Hz); 13C NMR (75 MHz, CDCl3) δ 147.64, 146.61, 144.97, 134.71, 129.09, 67.21, 63.13, 56.16, 38.97, 32.15, 31.82, 29.48, 28.10, 27.36, 26.55, 22.86, 21.97; Anal. Calcd for C19H34Br2N2.0.3H2O: C, 50.09; H, 7.63; N, 6.15. Found: C, 50.08; H, 7.64; N, 6.13. The mixture was heated at reflux for 3 days AcOH was evaporated the residue was recrystallized in ethyl acetate-CHCl3 to (S)-1-(7-methyl-octyl)-3-(1-methyl-pyrrolidin-2-yl)-pyridinium bromide hydrobromide salt (NONB-7M) (0.60 g, 58%) as hygroscopic white crystals

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 7-methyl-octan-1-ol (1.20 g, 8.33 mmol) in DMF (20 mL) was added triphenylphosphine (2.43 g, 9.26 mmol). The solution was cooled to 0° C. and NBS (1.60 g, 8.99 mmol) was added in portions. After stirring for 30 min at room temperature, the reaction was quenched with methanol (1 mL). The solution was diluted with ether (100 mL), washed with water, saturated aqueous NaHCO3 and brine successively. The organic layer was dried and concentrated. The residue was purified by flash chromatography on silica gel, eluting with hexane to afford 1-bromo-7-methyl-octane (1.28 g, 74%) as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 3.41 (2H, t, J=6.6 Hz), 1.85 (2H, m), 1.52 (1H, m), 1.42 (2H, m), 1.28 (4H, m), 1.17 (2H, m), 0.87 (3H, s), 0.85 (3H, s); 13C NMR (75 MHz, CDCl3) δ 39.16, 34.34, 33.14, 29.34, 28.52, 28.24, 27.51, 22.94. the reaction was quenched with methanol (1 mL) The solution was diluted with ether (100 mL) washed with water, saturated aqueous NaHCO3 and brine successively The organic layer was dried concentrated The residue was purified by flash chromatography on silica gel eluting with hexane