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

HRID 1784484Notes

Reaction equation

HRID 1784484 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, 31); 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-e941c7d8cd1b44b5a5fdf3c2ebce4d19
Source dataset
uspto-grants-2009_03
Patent number
US07504402B2

Reaction notes

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