Methylamine → 3-(4-methoxy-2-methylphenyl)4-methyl-5-(4-pentylbicyclo[2.2.2]oct-1-yl)4H-1,2,4-triazole

Reaction equation

COC1C=[CH:7][C:6]([C:9]2O[C:11]([C:14]34[CH2:21][CH2:20][C:17]([CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])([CH2:18][CH2:19]3)[CH2:16][CH2:15]4)=[N:12][N:13]=2)=[C:5]([CH3:27])[CH:4]=1.F[C:29](F)(F)[C:30]([O-:32])=O.[CH3:35][NH3+:36].[CH3:37]N>>[CH3:37][O:32][C:30]1[CH:29]=[CH:7][C:6]([C:9]2[N:36]([CH3:35])[C:11]([C:14]34[CH2:15][CH2:16][C:17]([CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])([CH2:20][CH2:21]3)[CH2:18][CH2:19]4)=[N:12][N:13]=2)=[C:5]([CH3:27])[CH:4]=1

Participants

Reactant 3

HCID 6329Methylamine

HCID 15260452Methylammonium trifluoroacetate

HCID 225916742-(4-Methoxy-2-methylphenyl)-5-(4-pentylbicyclo[2.2.2]oct-1-yl)-1,3,4-oxadiazole

Product 1

HCID 103624513-(4-methoxy-2-methylphenyl)4-methyl-5-(4-pentylbicyclo[2.2.2]oct-1-yl)4H-1,2,4-triazole

Procedure

2-(4-Methoxy-2-methylphenyl)-5-(4-pentylbicyclo[2.2.2]oct-1-yl)-1,3,4-oxadiazole (2-E) (988 mg, 2.68 mmol), methylammonium trifluoroacetate (9.72 g, 67 mmol, prepared by combining equimolar amounts of methylamine and trifluoroacetic acid in ether followed by concentration in vacuo), and methylamine (2M/MeOH, 33 mL, 67 mmol) were stirred together in a glass bomb at 150° C. for 114 h. The mixture was concentrated in vacuo and the residue partitioned with methylene chloride and water. The aqueous phase was extracted with methylene chloride and the combined extracts washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (silica gel, ethyl acetate:hexane, 7:3, then 9:1) to give 3-(4-methoxy-2-methylphenyl)-4-methyl-5-(4-pentylbicyclo[2.2.2]oct-1-yl)-4H-1,2,4-triazole (2-F). Mass spectrum: 382 (M+1); 1H NMR (500 MHz, CDCl3): δ 0.93 (t, 3H); 1.27 (m, 8H); 1.56 (m, 6H); 2.12 (m, 6H); 2.18 (s, 3H); 3.49 (s, 3H); 3.87 (s, 3H); 6.85 (m, 2H); 7.24 (d, 1H) ppm.