1H-1,2,4-Triazole → 1-(2,4-difluorophenyl)-1-(4-(2,4-difluorophenyl)thiazol-2-yl)-2-(1H-1,2,4-triazol-1-yl)ethanol

HRID 265327Notes

Reaction equation

HRID 265327 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([C:17]1[S:18][CH:19]=[C:20]([C:22]2SC=C(C(=O)N)N=2)C=1)([OH:16])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1.[NH:30]1C=NC=N1.[H-].[Na+].[F:37][C:38]1[CH:43]=[C:42]([F:44])C=[CH:40][C:39]=1C(C1SC=C(C2SC=C(C(OCC)=O)N=2)C=1)(O)CN1C=NC=N1>O.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([C:17]1[S:18][CH:19]=[C:20]([C:22]2[CH:40]=[CH:39][C:38]([F:37])=[CH:43][C:42]=2[F:44])[N:30]=1)([OH:16])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1

Participants

7

Reactant 4

HCID 92571H-1,2,4-TriazoleHCID 24758Sodium hydrideHCID 190651401-(2,4-difluorophenyl)-1-(4-(4-ethoxycarbonylthiazol-2-yl)-thiophen-2-yl)-2-(1H-1,2,4-triazol-1-yl)ethanolHCID 190651561-(2,4-difluorophenyl)-1-(4-(4-carbamoylthiazol-2-yl)-thiophen-2-yl)-2-(1H-1,2,4-triazol-1-yl)ethanol2×

Product 1

HCID 99100221-(2,4-difluorophenyl)-1-(4-(2,4-difluorophenyl)thiazol-2-yl)-2-(1H-1,2,4-triazol-1-yl)ethanol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

After 4-(2,4-difluorophenyl)thiazole (330 mg) was dissolved in diethyl ether (3 ml), and the resultant solution was cooled to -78° C. in a nitrogen atmosphere, a 1.6M solution (1.06 ml) of n-butyllithium in hexane was added, and the resultant mixture was stirred for about 10 minutes. After a solution of 2-chloro-2',4'-difluoroacetophenone (306 mg) in tetrahydrofuran was added dropwise to this mixture, the liquid reaction mixture was heated to -20° C. to add an aqueous solution of ammonium chloride. The reaction mixture was extracted with ethyl acetate. After drying an organic layer over magnesium sulfate, the solvent was distilled out under reduced pressure. The residue was dissolved in dimethylformamide (3 ml) to form a solution (A). On the other hand, a dimethylformamide solution (3 ml) (B) containing 1,2,4-triazole (350 ml) and 60% sodium hydride (135 mg) was prepared. The solution (B) was then added to the solution (A), and the mixture was heated at 60° C. for 6 hours. After ethyl acetate and water were added to the liquid reaction mixture, and an organic layer was washed several times with water, the solvent was distilled out. The residue was subjected to column chromatography on silica gel to recrystallize a fraction containing the intended compound from diethyl ether, thereby obtaining the title compound (390 mg). Its physical properties are shown in Table 1 which will be described subsequently.

Workup

  1. customwas prepared
  2. washan organic layer was washed several times with water
  3. distillationthe solvent was distilled out
  4. customto recrystallize a fraction
  5. additioncontaining the intended compound from diethyl ether

Sources & evidence

ORD record
ord-718b9e6a54174816a104a8b95ab7baaf
Source dataset
uspto-grants-1997_07
Patent number
US05648372

Reaction notes

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