Hydrogen Peroxide → Dibenzyl (2RS,3RS)-3-(4-[4-cyanophenyl]thiazol-2-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butyl phosphate

HRID 1006654Notes

Reaction equation

HRID 1006654 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([CH:14]([CH3:31])[C:15]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[F:30])([OH:22])[CH2:16][N:17]3[CH:21]=[N:20][CH:19]=[N:18]3)[S:12][CH:13]=2)=[CH:5][CH:4]=1)#[N:2].N1C=NN=N1.C(N(C(C)C)[P:41]([O:50][CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)(C)C.[OH:61]O>CN(C)C1C=CN=CC=1.C(Cl)Cl>[P:41]([O:22][C:15]([C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=1[F:30])([CH:14]([C:11]1[S:12][CH:13]=[C:9]([C:6]2[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)[N:10]=1)[CH3:31])[CH2:16][N:17]1[CH:21]=[N:20][CH:19]=[N:18]1)([O:42][CH2:43][C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)([O:50][CH2:51][C:52]1[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=1)=[O:61]

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 196621Bis(benzyloxy)(diisopropylamino)phosphineHCID 98459224-[2-[3-(2,4-Difluorophenyl)-3-hydroxy-4-(1,2,4-triazol-1-yl)butan-2-yl]-1,3-thiazol-4-yl]benzonitrileHCID 178418441HCID 178418441, compound

Product 1

HCID 86610195Dibenzyl (2RS,3RS)-3-(4-[4-cyanophenyl]thiazol-2-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butyl phosphateYield 51%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

3-[4-(4-Cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol (Example 88, EP 0667346, 900 mg, 2.06 mmol), 1H-tetrazole (432 mg, 6.18 mmol), 4-dimethylaminopyridine (100 mg, 0.82 mmol) and dibenzyl diisopropylphosphoramidite (1.42 g, 4.12 mmol) in methylene chloride (10 ml) were refluxed under a nitrogen atmosphere for 20 hours. The mixture was then cooled to 0° C., and hydrogen peroxide (2.5 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 (732 mg, 51%).

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-e70d2145cc894fefa0d58b6dc9274f82
Source dataset
uspto-grants-2004_09
Patent number
US06790957B2

Reaction notes

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