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

HRID 22832Notes

Reaction equation

HRID 22832 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

4

Reactant 3

HCID 6329MethylamineHCID 15260452Methylammonium trifluoroacetateHCID 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.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe residue partitioned with methylene chloride and water
  3. extractionThe aqueous phase was extracted with methylene chloride
  4. washthe combined extracts washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (silica gel, ethyl acetate

Sources & evidence

ORD record
ord-9c0ee73b1d5943d28e621ab3d9b46b7b
Source dataset
uspto-grants-2005_02
Patent number
US06849636B2

Reaction notes

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