Bromoacetonitrile → (R)-tert-butyl 3-((R)-(3-chloro-5-fluorophenyl)(cyanomethoxy)methyl)piperidine-1-carboxylate
Reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]([OH:23])[C@@H:10]2[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[H-].[Na+].Br[CH2:27][C:28]#[N:29]>CC#N>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]([O:23][CH2:27][C:28]#[N:29])[C@@H:10]2[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])[CH2:11]2)[CH:5]=[C:6]([F:8])[CH:7]=1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -20 °C
Procedure
To a solution of (R)-tert-butyl 3-((R)-(3-chloro-5-fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (3.5 g, 10.2 mmol) in CH3CN (140 mL), NaH (1.2 g, 30.6 mmol) was added at 0° C. The mixture was stirred for 1 hr. Then the mixture was cooled to −20° C., bromoacetonitrile (3.6 g, 30.6 mmol) was added dropwise. The mixture was allowed warm to 0° C. gradually. Another batch of NaH and bromoacetonitrile was added in the same manner. The mixture was quenched with H2O and extracted with CH2Cl2. The organic layer was dried over Na2SO4 and concentrate to give the crude (R)-tert-butyl 3-((R)-(3-chloro-5-fluorophenyl)(cyanomethoxy)methyl)piperidine-1-carboxylate (4.4, 100%).
Workup
- temperatureThe mixture was allowed warm to 0° C. gradually
- customThe mixture was quenched with H2O
- extractionextracted with CH2Cl2
- dry with materialThe organic layer was dried over Na2SO4
- concentrationconcentrate
Sources & evidence
- ORD record
- ord-273337744f504b7da96f3ee13b0e0aa9
- Source dataset
- uspto-grants-2013_07
- Patent number
- US08487108B2
Reaction notes
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