Tetrahydrofuran → Rac-2-chloro-4-[(2r,3r)-3-hydroxy-2,3,4,4-tetramethyl-5-oxopyrrolidin-1-yl]benzonitrile
Reaction equation
[Cl:1][C:2]1[CH:9]=[C:8]([N:10]2[CH:14]([CH3:15])[C:13](=[O:16])[C:12]([CH3:18])([CH3:17])[C:11]2=[O:19])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[Cl-].[NH4+].[CH2:22]1COCC1>>[Cl:1][C:2]1[CH:9]=[C:8]([N:10]2[C:11](=[O:19])[C:12]([CH3:18])([CH3:17])[C@:13]([OH:16])([CH3:22])[C@H:14]2[CH3:15])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]Participants
Procedure
A solution of 2-chloro-4-(3,3,5-trimethyl-2,4-dioxopyrrolidin-1-yl)benzonitrile (90 mg) in THF (5 mL) was cooled to −78° C., methylmagnesium bromide-ether solution (0.22 mL, 3 mol/L) was added under a nitrogen atmosphere, and the reaction mixture was warmed to room temperature. The reaction mixture was again cooled to −78° C., a 3 mol/L methylmagnesium bromide-ether solution (0.89 mL) was added, and the reaction mixture was warmed to room temperature. The reaction mixture was added to saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, and recrystallized from hexane-ethyl acetate to give the title compound as a colorless solid (yield: 29 mg, 30%).
Workup
- temperatureThe reaction mixture was again cooled to −78° C.
- temperaturethe reaction mixture was warmed to room temperature
- extractionthe mixture was extracted with ethyl acetate
- washThe extract was washed with saturated brine
- dry with materialdried over anhydrous magnesium sulfate
- concentrationconcentrated under reduced pressure
- customThe residue was purified by silica gel column chromatography
- customrecrystallized from hexane-ethyl acetate
Sources & evidence
- ORD record
- ord-9295944613b74f2b9f1f9dd7751c0b8e
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08420694B2
Reaction notes
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