Chlorosuccinimide → 1-(5-bromo-2-chlorophenyl)-N-(cyanomethyl)piperidine-2-carboxamide
Reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([N:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]2[C:14]([NH:16][CH2:17][C:18]#[N:19])=[O:15])[CH:5]=[CH:6][CH:7]=1.[Cl:20]N1C(=O)CCC1=O>C(O)(C)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:20])=[C:4]([N:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]2[C:14]([NH:16][CH2:17][C:18]#[N:19])=[O:15])[CH:3]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 60 °C
Procedure
To a suspension of 1-(3-bromophenyl)-N-(cyanomethyl)-2-piperidinecarboxamide (2.25 g, 6.98 mmol, prepared as described in example 25) in 70 mL of isopropyl alcohol was added N-chlorosuccinimide (1.02 g, 7.68 mmol). The suspension was heated to 60° C. and the resultant solution was stirred at 60° C. for 2 h. The mixture was cooled and partitioned between ethyl acetate and brine. The aqueous layer was extracted with ethyl acetate (3 ×) and the combined organic layers were dried over Na2SO4 and concentrated. Purification by flash chromatography (50% Et2O/hexanes) yielded 1-(5-bromo-2-chlorophenyl)-N-(cyanomethyl)piperidine-2-carboxamide (faster eluting compound) and 1-(3-bromo-4-chlorophenyl)-N-(cyanomethyl)piperidine-2-carboxamide (slower eluting compound).
Workup
- temperatureThe mixture was cooled
- custompartitioned between ethyl acetate and brine
- extractionThe aqueous layer was extracted with ethyl acetate (3 ×)
- dry with materialthe combined organic layers were dried over Na2SO4
- concentrationconcentrated
- customPurification by flash chromatography (50% Et2O/hexanes)
Sources & evidence
- ORD record
- ord-71fcc29006c041648107f4a18713011f
- Source dataset
- uspto-grants-2006_03
- Patent number
- US07012075B2
Reaction notes
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