4-Dimethylamino-4-(4-methoxy-phenyl)-1-methylamino-cyclohexane carbonitrile → HCID 44252839, compound

HRID 1477205Notes

Reaction equation

HRID 1477205 reaction equation
[CH3:1][N:2]([CH3:21])[C:3]1([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[CH2:8][CH2:7][C:6]([NH:11][CH3:12])([C:9]#N)[CH2:5][CH2:4]1>C(OCC)C>[CH3:20][O:19][C:16]1[CH:15]=[CH:14][C:13]([C:3]2([N:2]([CH3:21])[CH3:1])[CH2:4][CH2:5][C:6]([NH:11][CH3:12])([C:9]3[CH:7]=[CH:8][CH:3]=[CH:4][CH:5]=3)[CH2:7][CH2:8]2)=[CH:18][CH:17]=1

Participants

3

Reactant 1

HCID 686308414-Dimethylamino-4-(4-methoxy-phenyl)-1-methylamino-cyclohexane carbonitrile

Product 1

HCID 44252839HCID 44252839, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
35 °C

Procedure

Phenyl lithium (12.9 mL, 23.3 mmol, 1.8 M solution in dibutyl ether) was provided in argon and mixed in drops with a solution of the title compound from step 3 (2.23 g, 7.76 mmol) in abs. diethyl ether (30 mL) at RT. During this, the reaction solution heated to 35° C. and a solid separated out. The reaction mixture was stirred for 1 h with reflux (bath 50° C.), then hydrolysed in the ice bath (0-10° C.) with 20% NH4Cl solution (20 mL) and the organic phase was separated. The aqueous phase was extracted with ether (3×50 mL). The combined organic solutions were dried over Na2SO4 and concentrated to low volume in a vacuum. By means of flash chromatography (100 g silica gel) with ethyl acetate/methanol (20:1→9:1→MeOH→MeOH+2% NH3) the non-polar diastereoisomer was obtained in a mixed fraction with starting substance and ketone and lastly the polar diastereoisomer. The mixed fraction with non-polar diastereoisomer was purified again by flash chromatography with dichloromethane/methanol (50:1→20:1→9:1→4:1).

Workup

  1. customat RT
  2. customa solid separated out
  3. temperaturewith reflux (bath 50° C.)
  4. customhydrolysed in the ice bath (0-10° C.) with 20% NH4Cl solution (20 mL) and the organic phase was separated
  5. extractionThe aqueous phase was extracted with ether (3×50 mL)
  6. dry with materialThe combined organic solutions were dried over Na2SO4
  7. concentrationconcentrated to low volume in a vacuum
  8. customBy means of flash chromatography (100 g silica gel) with ethyl acetate/methanol (20:1→9:1→MeOH→MeOH+2% NH3) the non-polar diastereoisomer was obtained in a mixed fraction
  9. customThe mixed fraction with non-polar diastereoisomer was purified again by flash chromatography with dichloromethane/methanol (50:1→20:1→9:1→4:1)

Sources & evidence

ORD record
ord-db7f33bb6d1f4229b718623fd811faa2
Source dataset
uspto-grants-2016_08
Patent number
US09403767B2

Reaction notes

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