Diisopropylethylamine → N-[5-Chloro-4-(difluoromethyl)-2-nitrophenyl]-1-(tetrahydro-2H-pyran-4-yl)-4-piperidinamine
Reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](F)[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][C:3]=1[CH:12]([F:14])[F:13].C(N(CC)C(C)C)(C)C.Cl.Cl.[O:26]1[CH2:31][CH2:30][CH:29]([N:32]2[CH2:37][CH2:36][CH:35]([NH2:38])[CH2:34][CH2:33]2)[CH2:28][CH2:27]1>CN(C)C=O>[Cl:1][C:2]1[C:3]([CH:12]([F:14])[F:13])=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([NH:38][CH:35]2[CH2:34][CH2:33][N:32]([CH:29]3[CH2:30][CH2:31][O:26][CH2:27][CH2:28]3)[CH2:37][CH2:36]2)[CH:7]=1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 70 °C
Procedure
A stirred solution of 1-chloro-2-(difluoromethyl)-5-fluoro-4-nitrobenzene (D96, 200 mg, 0.89 mmol) in dimethylformamide (4 ml) at room temperature under argon was treated with N,N-diisopropylethylamine (0.47 ml, 2.7 mmol), followed by 1-(tetrahydro-2H-pyran-4-yl)-4-piperidinamine dihydrochloride (D40, 240 mg, 0.94 mmol) and then heated at 70° C. for 1.5 hrs. The reaction mixture was concentrated under vacuum and the residue treated with 10% Na2CO3 solution and extracted with ethyl acetate. The extract was dried and concentrated under vacuum to leave an orange solid. This was purified by chromatography on silica gel eluting with 0-20% methanol/ethyl acetate to afford the title compound as a yellow solid (330 mg, 96%).
Workup
- concentrationThe reaction mixture was concentrated under vacuum
- additionthe residue treated with 10% Na2CO3 solution
- extractionextracted with ethyl acetate
- customThe extract was dried
- concentrationconcentrated under vacuum
- customto leave an orange solid
- customThis was purified by chromatography on silica gel eluting with 0-20% methanol/ethyl acetate
Sources & evidence
- ORD record
- ord-330a5614aa4644b4a50887beb5371d1e
- Source dataset
- uspto-grants-2012_10
- Patent number
- US08288412B2
Reaction notes
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