Hydrochloric Acid → tert-Butyl 4-cyano-4-(3,4-dichlorophenyl)piperidine-1-carboxylate
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](F)=[CH:4][C:3]=1[Cl:9].[C:10]([CH:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1)#[N:11].C[Si]([N-][Si](C)(C)C)(C)C.[K+].Cl>C1(C)C=CC=CC=1>[C:10]([C:12]1([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([Cl:9])[CH:4]=2)[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1)#[N:11]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 60 °C
Procedure
To a solution of 1,2-dichloro-4-fluorobenzene (1.64 g, 10 mmol) in toluene (25 mL) was added tert-butyl 4-cyanopiperidine-1-carboxylate (2.10 g, 10 mmol) and KHMDS (0.5 M in toluene) (2.99 g, 15.00 mmol). The reaction mixture was stirred at 60° C. for 16 hours and cooled to room temperature. After the addition of 1N HCl (25 mL), the reaction mixture was extracted with EtOAc (3×20 mL). The combined organic extracts were washed with brine (100 mL), dried over MgSO4, filtered, and concentrated. The residue was purified by Prep-TLC (eluted with ethyl acetate:petroleum ether=1:5) to provide Example 140A. LCMS: 255 [M−100]+.
Workup
- temperaturecooled to room temperature
- extractionthe reaction mixture was extracted with EtOAc (3×20 mL)
- washThe combined organic extracts were washed with brine (100 mL)
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated
- customThe residue was purified by Prep-TLC (eluted with ethyl acetate:petroleum ether=1:5)
- customto provide Example 140A
Sources & evidence
- ORD record
- ord-ca4c637b6dd04b5e9b0c779da958ec1d
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08772500B2
Reaction notes
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