Sodium hydride → 2-Fluoro-5-((1s,2s,5s)-6,6-dimethylbicyclo[3.1.1]hept-2-ylmethoxy)benzonitrile
Reaction equation
[CH3:1][C:2]1([CH3:11])[C@H:7]2[CH2:8][C@@H:3]1[CH2:4][CH2:5][C@@H:6]2[CH2:9][OH:10].[H-].[Na+].[F:14][C:15]1[CH:22]=[CH:21][CH:20]=[C:19](F)[C:16]=1[C:17]#[N:18]>CN(C)C=O>[F:14][C:15]1[CH:22]=[CH:21][C:20]([O:10][CH2:9][C@H:6]2[CH2:5][CH2:4][C@H:3]3[CH2:8][C@@H:7]2[C:2]3([CH3:11])[CH3:1])=[CH:19][C:16]=1[C:17]#[N:18]Participants
Procedure
A solution of (1S,2S,5S)-(−)-myrtanol (1.0 g, 6.48 mmol) in dimethylformamide was added to a cooled (0° C.) slurry of sodium hydride (310 mg, 7.78 mmol) in dimethylformamide under nitrogen atmosphere. The reaction mixture was slowly warmed to room temperature, stirred for 1 hour. Again, cooled (0° C.), then a solution of 2,6-difluorobenzonitrile (1.08 g, 7.78 mmol) in dimethylfomamide was added, stirred overnight at room temperature. The reaction mixture was poured on crushed-ice water, stirred. The reaction mixture was extracted with ethyl acetate, dried, filtered and concentrated. Purification by silica gel chromatography (1:1 hexanes in dichloromethane) yielded 1.36 g of 2-fluoro-5-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-ylmethoxy)benzonitrile.
Workup
- temperatureAgain, cooled (0° C.)
- stirringstirred overnight at room temperature
- additionThe reaction mixture was poured
- stirringstirred
- extractionThe reaction mixture was extracted with ethyl acetate
- customdried
- filtrationfiltered
- concentrationconcentrated
- customPurification by silica gel chromatography (1:1 hexanes in dichloromethane)
Sources & evidence
- ORD record
- ord-e2842b8c3c3f445985f6c2ba57f83ed1
- Source dataset
- uspto-grants-2011_02
- Patent number
- US07888366B2
Reaction notes
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