Nicotine → (s)-1-(7-Methyl-octyl)-3-(1-methyl-pyrrolidin-2-yl)-pyridinium bromide hydrobromide salt

HRID 9824

Reaction equation

HRID 9824 reaction equation
[N:1]1[CH:6]=[C:5]([C@@H:7]2[CH2:12][CH2:11][CH2:10][N:8]2[CH3:9])[CH:4]=[CH:3][CH:2]=1.[Br:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH:20]([CH3:22])[CH3:21]>CC(O)=O>[BrH:13].[Br-:13].[CH3:21][CH:20]([CH3:22])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][N+:1]1[CH:2]=[CH:3][CH:4]=[C:5]([C@@H:7]2[CH2:12][CH2:11][CH2:10][N:8]2[CH3:9])[CH:6]=1

Participants

4

Reactant 2

HCID 89594NicotineHCID 136347811-Bromo-7-methyloctane

Product 1

HCID 69596214(s)-1-(7-Methyl-octyl)-3-(1-methyl-pyrrolidin-2-yl)-pyridinium bromide hydrobromide salt

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

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.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 3 days
  3. customAcOH was evaporated
  4. customthe 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

Sources & evidence

ORD record
ord-1fe6ce655e6c48aab8e8d39e3535dc10
Source dataset
uspto-grants-2006_08
Patent number
US07091357B2

Linked notes

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