Nicotine → (S)-1-(6-cyclohexyl-hexyl)-3-(1-methyl-pyrrolidin-2-yl)-pyridinium bromide hydrobromide salt

HRID 9813Notes

Reaction equation

HRID 9813 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]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1>CC(O)=O>[BrH:13].[Br-:13].[CH:20]1([CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][N+:1]2[CH:2]=[CH:3][CH:4]=[C:5]([C@@H:7]3[CH2:12][CH2:11][CH2:10][N:8]3[CH3:9])[CH:6]=2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

4

Reactant 2

HCID 89594NicotineHCID 21988677(6-Bromo-hexyl)-cyclohexane

Product 1

HCID 69596284(S)-1-(6-cyclohexyl-hexyl)-3-(1-methyl-pyrrolidin-2-yl)-pyridinium bromide hydrobromide saltYield 63.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a stirred solution of (S)-nicotine (0.31 g, 1.9 mmol) in AcOH (8 ml) was added (6-bromo-hexyl)-cyclohexane (1.15 g, 4.65 mmol). The mixture was heated at reflux for 3 days. AcOH was evaporated and the residue was recrystallized in ethyl acetate-CHCl3 to afford (S)-1-(6-cyclohexyl-hexyl)-3-(1-methyl-pyrrolidin-2-yl)-pyridinium bromide hydrobromide salt (NCyNB-6) (0.59 g, 63%) as hygroscopic white crystals: 1H NMR (300 MHz, CDCl3) δ 11.71 (1H, s), 10.44 (1H, s), 9.58 (1H, d, J=8.1 Hz), 9.04 (1H, d, J=6.0 Hz), 8.29 (1H, dd, J=7.8, 6.0 Hz), 5.75 (1H, m), 4.78 (2H, m), 4.02 (1H, m), 3.37 (1H, m), 2.98 (3H, d, J=4.8 Hz), 2.75 (1H, m), 2.48 (3H, m), 2.13 (2H, m), 1.65 (5H, m), 1.05–1.45 (12H, m), 0.83 (2H, m), 13C NMR (75 MHz, CDCl3) δ 147.66, 146.65, 144.57, 134.85, 128.93, 67.09, 63.11, 56.09, 38.71, 37.77, 37.52, 33.61, 32.09, 31.80, 29.53, 26.92, 26.84, 26.63, 26.54, 21.89; Anal. Calcd for C22H38Br2N2.0.3H2O: C, 53.30; H, 7.85; N, 5.65. Found: C, 53.35; H, 7.74; N, 5.70.

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

Sources & evidence

ORD record
ord-cfc236aa65134edd94b1a22bfd257aac
Source dataset
uspto-grants-2006_08
Patent number
US07091357B2

Reaction notes

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