Bromoacetonitrile → (R)-tert-butyl 3-((R)-(cyanomethoxy)(5-fluoro-2-methylphenyl)methyl)piperidine-1-carboxylate
Reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:23])=[C:6]([C@H:8]([OH:22])[C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]2)[CH:7]=1.[H-].[Na+].Br[CH2:27][C:28]#[N:29]>CC#N>[C:28]([CH2:27][O:22][C@@H:8]([C:6]1[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=1[CH3:23])[C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:10]1)#[N:29]Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -40 °C
Procedure
To a solution of (R)-tert-butyl 3-((R)-(5-fluoro-2-methylphenyl)(hydroxy)methyl)piperidine-1-carboxylate (1.2 g, 0.0037 mol) in MeCN (20 mL), NaH (0.27 g, 0.011 mol) was added at 0° C. The mixture was stirred for 1 hr followed by cooling to −40° C. and adding bromoacetonitrile (1.3 g, 0.011 mol) in portions. The mixture was stirred for 0.5 hour at −20° C. The reaction was quenched with H2O. The mixture was extracted with CH2Cl2. The organic layer was dried by Na2SO4, concentrate to get the target molecule (R)-tert-butyl 3-((R)-(cyanomethoxy)(5-fluoro-2-methylphenyl)methyl)piperidine-1-carboxylate (1.2 g, 90%).
Workup
- stirringThe mixture was stirred for 0.5 hour at −20° C
- customThe reaction was quenched with H2O
- extractionThe mixture was extracted with CH2Cl2
- dry with materialThe organic layer was dried by Na2SO4
- concentrationconcentrate
Sources & evidence
- ORD record
- ord-48a6c26db89d4f6ab40d89a5ea273f7a
- Source dataset
- uspto-grants-2013_07
- Patent number
- US08487108B2
Reaction notes
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