Triethylamine → N,N-dimethyl-1-(2-nitro-4-(trifluoromethyl)phenyl)piperidin-4-amine

HRID 1042681Notes

Reaction equation

HRID 1042681 reaction equation
Cl.Cl.C(N1CCC(N(C)C)CC1)C1C=CC=CC=1.Cl.Cl.[CH3:21][N:22]([CH3:29])[CH:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1.F[C:31]1[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][C:32]=1[N+:41]([O-:43])=[O:42].C(N(CC)CC)C>[Pd].O.C1COCC1.CO>[CH3:21][N:22]([CH3:29])[CH:23]1[CH2:28][CH2:27][N:26]([C:31]2[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:38])[F:39])=[CH:33][C:32]=2[N+:41]([O-:43])=[O:42])[CH2:25][CH2:24]1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 677784-Fluoro-3-nitrobenzotrifluorideHCID 225914404-(Dimethylamino)piperidine dihydrochlorideHCID 231533931-benzyl-N,N-dimethylpiperidin-4-amine dihydrochloride

Product 1

HCID 16109041N,N-dimethyl-1-(2-nitro-4-(trifluoromethyl)phenyl)piperidin-4-amine

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To 1-benzyl-N,N-dimethylpiperidin-4-amine dihydrochloride (6.7 g, 23 mmol) was added Pd/C (10%, 2.4 g) under argon. Methanol (100 ml) was added via syringe, and H2 gas was introduced and the mixture stirred vigorously under an atmosphere of H2. After 48 h, the mixture was flushed with nitrogen, filtered through celite and concentrated to afford a mixture of starting material and N,N-dimethylpiperidin-4-amine dihydrochloride as a white solid. This solid was treated with 1-Fluoro-2-nitro-4-trifluoromethyl-benzene (3.2 ml, 22.9 mmol), triethylamine (12.7 ml, 92 mmol), and 50 ml dry THF. The mixture was heated to 75° C. with a water-cooled reflux condenser for 12 h. The mixture was allowed to cool to ambient temperature, was filtered through a fritted funnel, and concentrated to an orange oil. The residue was purified by silica gel chromatography (MC/MeOH/conc. NH4OH) to give the desired product as an orange oil. MS (m/z): 318.1 (M+H)+. Calc'd for C14H18F3N3O2: 317.31.

Workup

  1. additionH2 gas was introduced
  2. customthe mixture was flushed with nitrogen
  3. filtrationfiltered through celite
  4. concentrationconcentrated
  5. customto afford
  6. temperaturecooled
  7. temperaturereflux condenser for 12 h
  8. filtrationwas filtered through a fritted funnel
  9. concentrationconcentrated to an orange oil
  10. customThe residue was purified by silica gel chromatography (MC/MeOH/conc. NH4OH)

Sources & evidence

ORD record
ord-397d90546d184251ab9777be06ecdf5f
Source dataset
uspto-grants-2013_10
Patent number
US08557996B2

Reaction notes

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