Methyl morpholine oxide → 5-{4-[5-(2-chloro-4-hydroxyphenyl)-4-methyl-4H-1,2,4-triazol-3-yl]bicyclo[2.2.2]oct-1-yl}pentan-2-one

HRID 22845Notes

Reaction equation

HRID 22845 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:28])[CH:5]=[CH:6][C:7]=1[C:8]1[N:12]=[C:11]([C:13]23[CH2:20][CH2:19][C:16]([CH2:21][CH2:22][CH2:23][CH:24]([OH:26])[CH3:25])([CH2:17][CH2:18]2)[CH2:15][CH2:14]3)[N:10](C)[N:9]=1.[CH3:29][N+]1([O-])CCOCC1>C(Cl)Cl.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[Cl:1][C:2]1[CH:3]=[C:4]([OH:28])[CH:5]=[CH:6][C:7]=1[C:8]1[N:12]([CH3:29])[C:11]([C:13]23[CH2:18][CH2:17][C:16]([CH2:21][CH2:22][CH2:23][C:24](=[O:26])[CH3:25])([CH2:15][CH2:14]2)[CH2:19][CH2:20]3)=[N:10][N:9]=1

Participants

5

Reactant 2

HCID 82029Methyl morpholine oxideHCID 1358707353-Chloro-4-{5-[4-(4-hydroxypentyl)bicyclo[2.2.2]oct-1-yl]-1-methyl-1-H-1,2,4-triazol-3-yl}phenol

Product 1

HCID 1354244525-{4-[5-(2-chloro-4-hydroxyphenyl)-4-methyl-4H-1,2,4-triazol-3-yl]bicyclo[2.2.2]oct-1-yl}pentan-2-one

Reagents, catalysts & solvents 2

HCID 178419074HCID 178419074, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

3-Chloro-4-{5-[4-(4-hydroxypentyl)bicyclo[2.2.2]oct-1-yl]-4-methyl-4H-1,2,4-triazol-3-yl}phenol (5-K) (0.0035 g, 0.00869 mmol) was stirred in 0.5 mL of dry methylene chloride over activated 4 Å sieves. N-methylmorpholine N-oxide (0.0015 g, 0.013 mmol) was added. The mixture was allowed to stir under N2 for 15 min. Tetrapropylammonium perruthenate (0.00112 g, 0.00956 mmol) was added and the reaction was allowed to stir for 2 h. The mixture was filtered through celite filtering agent. The product, 5-{4-[5-(2-chloro-4-hydroxyphenyl)-4-methyl4H-1,2,4-triazol-3-yl]bicyclo[2.2.2]oct-1-yl}pentan-2-one (6-L), was purified by preparative reverse phase HPLC on a C-18 silica gel column using a gradient of acetonitrile-water buffered with 0.1% trifluoroacetic acid. The effluent containing the pure triazole was basified with 10% NaHCO3, evaporated in vacuo to remove most of the acetonitrile, and extracted with methylene chloride. The organic extract was dried (MgSO4) and evaporated, and the residue dried under vacuum to provide the desired compound. MS (ESI+)=402.3 (M+1).

Workup

  1. stirringto stir for 2 h
  2. filtrationThe mixture was filtered through celite filtering agent
  3. customThe product, 5-{4-[5-(2-chloro-4-hydroxyphenyl)-4-methyl4H-1,2,4-triazol-3-yl]bicyclo[2.2.2]oct-1-yl}pentan-2-one (6-L), was purified by preparative reverse phase HPLC on a C-18 silica gel column
  4. additionThe effluent containing the pure triazole
  5. customevaporated in vacuo
  6. customto remove most of the acetonitrile
  7. extractionextracted with methylene chloride
  8. extractionThe organic extract
  9. dry with materialwas dried (MgSO4)
  10. customevaporated
  11. customthe residue dried under vacuum

Sources & evidence

ORD record
ord-659fff01bc8f475c9555a5f2702417fa
Source dataset
uspto-grants-2005_02
Patent number
US06849636B2

Reaction notes

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