Sodium ethanethiolate → 3-Chloro-4-{5-[4-(4-hydroxypentyl)bicyclo[2.2.2]oct-1-yl]-1-methyl-1-H-1,2,4-triazol-3-yl}phenol

HRID 1784496Notes

Reaction equation

HRID 1784496 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8]C)[CH:5]=[CH:4][C:3]=1[C:10]1[N:14](C)[N:13]=[C:12]([C:16]23[CH2:23][CH2:22][C:19]([CH2:24][CH2:25][CH2:26][CH:27]([OH:29])[CH3:28])([CH2:20][CH2:21]2)[CH2:18][CH2:17]3)[N:11]=1.[CH2:30]([S-])C.[Na+]>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[C:10]1[N:11]=[C:12]([C:16]23[CH2:23][CH2:22][C:19]([CH2:24][CH2:25][CH2:26][CH:27]([OH:29])[CH3:28])([CH2:18][CH2:17]2)[CH2:20][CH2:21]3)[N:13]([CH3:30])[N:14]=1

Participants

4

Reactant 2

HCID 4459711Sodium ethanethiolate2×HCID 865933835-{4-[5-(2-Chloro-4-methoxyphenyl)-1-methyl-1-H-1,2,4-triazol-3-yl]bicyclo[2.2.2]oct-1-yl}pentan-2-ol

Product 1

HCID 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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-{4-[5-(2-Chloro-4-methoxyphenyl)-1-methyl-1-H-1,2,4-triazol-3-yl]bicyclo[2.2.2]oct-1-yl}pentan-2-ol (5-J) (0.036 g, 0.086 mmol) was placed in a small vial with 0.5 mL of DMF. Sodium ethanethiolate (0.0218 g, 0.260 mmol) was added to the solution. The vial was sealed and heated to 1000 C for 1.5 h. The incomplete reaction required another 1.5 equivalents of sodium ethanethiolate (0.011 g). The vial was resealed and heated at 1000 C for 1 h. The product, 3-chloro-4-{5-[4-(4-hydroxypentyl)bicyclo[2.2.2]oct-1-yl]-1-methyl-1-H-1,2,4-triazol-3-yl}phenol (5-K) 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 made basic 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+)=404.4 (M+1).

Workup

  1. customThe vial was sealed
  2. temperatureheated to 1000 C for 1.5 h
  3. customThe incomplete reaction
  4. temperatureheated at 1000 C for 1 h
  5. customThe product, 3-chloro-4-{5-[4-(4-hydroxypentyl)bicyclo[2.2.2]oct-1-yl]-1-methyl-1-H-1,2,4-triazol-3-yl}phenol (5-K) was purified by preparative reverse phase HPLC on a C-18 silica gel column
  6. additionThe effluent containing the pure triazole
  7. customevaporated in vacuo
  8. customto remove most of the acetonitrile
  9. extractionextracted with methylene chloride
  10. extractionThe organic extract
  11. dry with materialwas dried (MgSO4)
  12. customevaporated
  13. customthe residue dried under vacuum

Sources & evidence

ORD record
ord-df60b65268cd4187bb8abcd94d317da8
Source dataset
uspto-grants-2009_03
Patent number
US07504402B2

Reaction notes

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