Tetrahydrofuran → (R)-2-Methyl-propane-2-sulfinic acid [(R)-1-(4-chloro-3,5-dimethyl-phenyl)-propyl]-amide
Reaction equation
[Cl:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5](/[CH:9]=[N:10]/[S@@:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[O:12])=[CH:4][C:3]=1[CH3:17].[CH2:18]1COC[CH2:19]1>>[Cl:1][C:2]1[C:3]([CH3:17])=[CH:4][C:5]([C@H:9]([NH:10][S@@:11]([C:13]([CH3:14])([CH3:16])[CH3:15])=[O:12])[CH2:18][CH3:19])=[CH:6][C:7]=1[CH3:8]Participants
3
Procedure
In a separate flask a solution of INT 36 (3.5 g, 12.88 mmol) in THF (100 mL) was cooled in a dry ice bath under argon to −78° C. At this temperature the organozincate solution from above was added dropwise over a period of about 30 minutes. Stirring was continued for another 90 minutes before the resulting mixture was first quenched carefully with 10% ammonium chloride solution (40 mL), then water (50 mL). The reaction mixture was allowed to warm up to room temperature and was then extracted with Et2O (200 mL). The organic layer was washed with water and brine, dried over sodium sulfate, filtered and concentrated. The crude was purified by chromatography on silica gel (cyclohexane/EtOAc).
Workup
- additionAt this temperature the organozincate solution from above was added dropwise over a period of about 30 minutes
- customwas first quenched carefully with 10% ammonium chloride solution (40 mL)
- extractionwas then extracted with Et2O (200 mL)
- washThe organic layer was washed with water and brine
- dry with materialdried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customThe crude was purified by chromatography on silica gel (cyclohexane/EtOAc)
Sources & evidence
- ORD record
- ord-84c6cffe36c9422cbefc591b734cb5f5
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08791100B2
Reaction notes
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