Dimethylformamide → (S)-2-(difluoromethyl)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)benzaldehyde
Reaction equation
Br[C:2]1[CH:16]=[CH:15][C:5]([O:6][CH2:7][C@H:8]2[CH2:12][O:11][C:10]([CH3:14])([CH3:13])[O:9]2)=[CH:4][C:3]=1[CH:17]([F:19])[F:18].[Li]CCCC.CN([CH:28]=[O:29])C.[NH4+].[Cl-]>C1COCC1>[F:18][CH:17]([F:19])[C:3]1[CH:4]=[C:5]([O:6][CH2:7][C@H:8]2[CH2:12][O:11][C:10]([CH3:14])([CH3:13])[O:9]2)[CH:15]=[CH:16][C:2]=1[CH:28]=[O:29]Participants
Procedure
To a solution of (S)-4-((4-bromo-3-(difluoromethyl)phenoxy)methyl)-2,2-dimethyl-1,3-dioxolane (65; 3 g, 0.089 mol) in THF (30 ml) was added n-BuLi (2.5M solution in hexane, 3.9 ml, 0.097 mol) at −78° C. The mixture was stirred at the same temperature for 1 h and DMF (0.929 g, 0.103 mol) was added dropwise. After stirring at −78° C. for an additional 20 min, saturated aqueous NH4Cl (30 ml) was added. The resulting reaction mixture was warmed to room temperature and extracted with Et2O (3×15 mL). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. The resulting residue was purified by chromatography (petroleum ether/EtOAc=5:1) to afford the titled compound, namely (S)-2-(difluoromethyl)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)benzaldehyde 66 (1.83 g, 72%).
Workup
- stirringAfter stirring at −78° C. for an additional 20 min
- customThe resulting reaction mixture
- extractionextracted with Et2O (3×15 mL)
- dry with materialThe combined organic layers were dried (Na2SO4)
- concentrationconcentrated under reduced pressure
- customThe resulting residue was purified by chromatography (petroleum ether/EtOAc=5:1)
Sources & evidence
- ORD record
- ord-793e8ffba69449a78d8ba83602d0739d
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08846947B2
Reaction notes
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