N-[4-chloro-2-methyl-3-(trifluoromethyl)phenyl]-2,2-dimethylpropanamide → N-(4-cyano-2-methyl-3-(trifluoromethyl)phenyl)pivalamide
Reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[C:4]([CH3:15])[C:3]=1[C:16]([F:19])([F:18])[F:17].[Cu](C#N)[C:21]#[N:22]>CN1C(=O)CCC1.CCOC(C)=O.O>[C:21]([C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[C:4]([CH3:15])[C:3]=1[C:16]([F:19])([F:18])[F:17])#[N:22]Participants
6
Reactant 2
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 200 °C
Procedure
A solution of N-[4-chloro-2-methyl-3-(trifluoromethyl)phenyl]-2,2-dimethylpropanamide (0.257 g, 0.875 mmol) in NMP (2.5 mL) was treated with copper cyanide (0.180 g, 2.01 mmol) and the resulting suspension was heated to 200° C. in a microwave for 14 h. The cooled reaction mixture was diluted with EtOAc and water and then filtered through a pad of celite. The filtrate was concentrated to a brown oil and then partitioned between Et2O and water. The aqueous portion was further extracted with Et2O and the combined organics were dried (Na2SO4), filtered, and concentrated to a brown foam. Trituration with hexanes/Et2O afforded the title compound (0.222 g) in good purity: MS (ES) m/z 285 (M+1).
Workup
- customThe cooled reaction mixture
- filtrationfiltered through a pad of celite
- concentrationThe filtrate was concentrated to a brown oil
- custompartitioned between Et2O and water
- extractionThe aqueous portion was further extracted with Et2O
- dry with materialthe combined organics were dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated to a brown foam
Sources & evidence
- ORD record
- ord-afe8fb9ea13249d0825734ab7ac9aa2a
- Source dataset
- uspto-grants-2014_03
- Patent number
- US08673948B2
Reaction notes
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