4-Benzyl-4-dimethylaminomethyl-1-methylamino-cyclohexane carbonitrile → 4-benzyl-4-((dimethylamino)methyl)-N-methyl-1-phenylcyclohexanamine

HRID 76933Notes

Reaction equation

HRID 76933 reaction equation
[C:1]1([Li])[CH:6]=[CH:5]C=[CH:3][CH:2]=1.[CH2:8]([C:15]1([CH2:25][N:26]([CH3:28])[CH3:27])[CH2:20][CH2:19][C:18]([NH:23][CH3:24])([C:21]#N)[CH2:17][CH2:16]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C(OCC)C>[CH2:8]([C:15]1([CH2:25][N:26]([CH3:27])[CH3:28])[CH2:16][CH2:17][C:18]([C:21]2[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=2)([NH:23][CH3:24])[CH2:19][CH2:20]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

4

Reactant 2

HCID 686305894-Benzyl-4-dimethylaminomethyl-1-methylamino-cyclohexane carbonitrileHCID 178506676HCID 178506676, compound

Product 1

HCID 686322714-benzyl-4-((dimethylamino)methyl)-N-methyl-1-phenylcyclohexanamine

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Phenyl lithium (33 mL, 60 mmol, 1.8 M solution in dibutyl ether) was mixed in drops with a solution of the title compound from step 1 (5.70 g, 20 mmol) in diethyl ether (60 mL) in argon and at room temperature. During this, the temperature of the reaction solution rose to 35° C. and a solid separated out. The reaction mixture was stirred with reflux for 30 min, then hydrolysed in an ice bath with 20% NH4Cl solution (40 mL) and the organic phase was separated. The aqueous phase was extracted with ether (3×100 mL). The combined organic phases were dried over Na2SO4, filtered and concentrated to low volume in a vacuum. The residue was purified by flash chromatography with chloroform/methanol (20:1→9:1→1:1→1% TEA). The polar diastereomer was obtained in clean form. The non-polar diastereomer was isolated in impure state.

Workup

  1. customrose to 35° C.
  2. customa solid separated out
  3. temperaturewith reflux for 30 min
  4. customhydrolysed in an ice bath with 20% NH4Cl solution (40 mL)
  5. customthe organic phase was separated
  6. extractionThe aqueous phase was extracted with ether (3×100 mL)
  7. dry with materialThe combined organic phases were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to low volume in a vacuum
  10. customThe residue was purified by flash chromatography with chloroform/methanol (20:1→9:1→1:1→1% TEA)
  11. customThe polar diastereomer was obtained in clean form
  12. customThe non-polar diastereomer was isolated in impure state

Sources & evidence

ORD record
ord-728e785bc4534674bc06dc122059bc31
Source dataset
uspto-grants-2014_09
Patent number
US08835689B2

Reaction notes

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