Hydrogen Peroxide → HCID 22266795, compound

HRID 489475Notes

Reaction equation

HRID 489475 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:38])([CH2:32][N:33]1[CH:37]=[N:36][CH:35]=[N:34]1)[CH2:10][N:11]1[CH:15]=[N:14][C:13](/[CH:16]=[CH:17]/[C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]([F:31])([F:30])[CH:27]([F:29])[F:28])=[CH:20][CH:19]=2)=[N:12]1.N1C=NN=N1.C(N(C(C)C)[P:48]([O:57][CH2:58][C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)[O:49][CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)(C)C.[OH:68]O>C(Cl)Cl>[P:48]([O:38][C:9]([C:3]1[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=1[F:1])([CH2:32][N:33]1[CH:37]=[N:36][CH:35]=[N:34]1)[CH2:10][N:11]1[CH:15]=[N:14][C:13](/[CH:16]=[CH:17]/[C:18]2[CH:19]=[CH:20][C:21]([O:24][CH2:25][C:26]([F:31])([F:30])[CH:27]([F:28])[F:29])=[CH:22][CH:23]=2)=[N:12]1)([O:49][CH2:50][C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1)([O:57][CH2:58][C:59]1[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=1)=[O:68]

Participants

6

Reactant 4

HCID 784Hydrogen PeroxideHCID 196621Bis(benzyloxy)(diisopropylamino)phosphineHCID 100301472-(2,4-Difluorophenyl)-1-(3-{(E)-2-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]vinyl}-1H-1,2,4-triazol-1-yl)-3-(1H-1,2,4-triazol-1-yl)-2-propanolHCID 178418441HCID 178418441, compound

Product 1

HCID 22266795HCID 22266795, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

2-(2,4-Difluorophenyl)-1-{3-[(E)-4-(2,2,3,3-tetrafluoropropoxy)styryl]-1H-1,2,4-triazol-1-yl}-3-(1H-1,2,4-triazol-1-yl)propan-2-ol (the racemate of Example 19, EP 0472392, 475 mg, 0.88 mmol), 1H-tetrazole (185 mg, 2.64 mmol) and dibenzyl diisopropylphosphoramidite (607 mg, 1.76 mmol) in methylene chloride (5 ml) was stirred at room temperature under a nitrogen atmosphere for 20 hours. The mixture was then cooled to 0° C., and hydrogen peroxide (1.0 ml, 30% solution in water) was added dropwise maintaining the temperature below 20° C. The resulting mixture was stirred at 20° C. for 30 minutes before separating the organic layer, which was washed with water, dried (MgSO4) and the solvent evaporated. The resulting pale yellow oil was purified by column chromatography (silica gel, eluting with ethyl acetate/hexane) to give the subtitle compound as a viscous syrup (595 mg, 84%).

Workup

  1. temperaturemaintaining the temperature below 20° C
  2. custombefore separating the organic layer, which
  3. washwas washed with water
  4. dry with materialdried (MgSO4)
  5. customthe solvent evaporated
  6. customThe resulting pale yellow oil was purified by column chromatography (silica gel, eluting with ethyl acetate/hexane)

Sources & evidence

ORD record
ord-7e951a8cabcf4f9c82233310d5116b52
Source dataset
uspto-grants-2005_12
Patent number
US06977302B2

Reaction notes

Loading…