Isopropanol → (alphaR,betaR)-beta-(2,5-Difluorophenyl)-beta-hydroxy-alpha-methyl-1H-1,2,4-triazole-1-butanethioamide
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@@:9]([OH:20])([CH2:14][N:15]1[CH:19]=[N:18][CH:17]=[N:16]1)[C@@H:10]([CH3:13])[C:11]#[N:12].P([O-])(OCC)(SCC)=[S:22].C(O)(C)C.C([O-])([O-])=O.[Na+].[Na+]>O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@@:9]([OH:20])([CH2:14][N:15]1[CH:19]=[N:18][CH:17]=[N:16]1)[C@@H:10]([CH3:13])[C:11]([NH2:12])=[S:22]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 110 °C
Procedure
(2S,3R)-3-(2,5-Difluoro-phenyl)-3-hydroxy-2-methyl-4-[1,2,4]triazol-1-yl-butyronitrile (50.0 g, 180 mmol), diethyl dithiophosphate (134 mL, 719 mmol), isopropanol (50 mL) and water (40 mL) were mixed together and the mixture was heated in an oil-bath (temp. setting at 110° C.) for 3 h. After cooling to 0° C., 5% Na2CO3 aqueous solution (500 mL) was added slowly and then solid Na2CO3 (25 g) was added portionwise. The mixture was extracted with EtOAc (1 L) and the EtOAc layer was washed with sat. NaHCO3 aqueous solution, water (×2) and brine, dried over MgSO4 and evaporated under reduce pressure. The resulting solid was purified by recrystalization from isopropanol to give pure (2R,3R)-3-(2,5-difluoro-phenyl)-3-hydroxy-2-methyl-4-[1,2,4]triazol-1-ylthiobutyrarnide (47.9 g, 85%).
Workup
- temperatureAfter cooling to 0° C.
- extractionThe mixture was extracted with EtOAc (1 L)
- washthe EtOAc layer was washed with sat. NaHCO3 aqueous solution, water (×2) and brine
- dry with materialdried over MgSO4
- customevaporated
- customThe resulting solid was purified by recrystalization from isopropanol
Sources & evidence
- ORD record
- ord-4c9990ef87f64e5fbf38215bad34084d
- Source dataset
- uspto-grants-2001_10
- Patent number
- US06300353B1
Reaction notes
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