Hydrochloric Acid → HCID 12052797, compound

HRID 1825883Notes

Reaction equation

HRID 1825883 reaction equation
[NH2:1][C@H:2]([CH2:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1)[C:3]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[O:17][CH3:18])[CH2:7][CH2:6]1)=O.Cl>C1(C)C=CC=CC=1.O.C(OCC)C>[CH:20]1([CH2:19][C@@H:2]([NH2:1])[CH2:3][N:5]2[CH2:10][CH2:9][N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:17][CH3:18])[CH2:7][CH2:6]2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 69652439HCID 69652439, compound

Product 1

HCID 12052797HCID 12052797, compoundYield 99.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 3283Diethyl EtherSolvent

Procedure

The above-described desired (R)-2-amino-3-cyclohexyl-1-[4-(2-methoxyphenyl)-piperazin-1-yl]-propan-1-one (0.83 g, 2.25 mmol) was dissolved in 20 ml of dry toluene and placed in a flame-dried flask under a nitrogen atmosphere. The mixture was heated to reflux and a solution of 0.45 mL of 10M borane-dimethylsulfide complex in 15 mL of dry toluene was added dropwise over ten minutes as reflux was maintained. After complete addition, the reaction mixture was refluxed an additional two hours. The reaction was then cooled to room temperature and 30 mL of 1N aq. HCl was added and the mixture stirred for one hour. Stirring was halted, the mixture was diluted with 20 mL of water and 20 mL of diethyl ether, and the layers were separated. The aqueous layer was washed with an additional 30 mL portion of diethyl ether and then made basic by addition of 50% aq. sodium hydroxide solution. The basic aqueous mixture was then extracted with three 50 mL portions of dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate and concentrated on a rotary evaporator to yield the desired {(1R)-1-cyclohexylmethyl-2-[4-(2-methoxyphenyl)-piperazin-1-yl]-ethyl}-amine (0.74 g, 93% yield) as a yellow oil, which was pure enough to use in subsequent experiments; MS (+) ESI m/z=(M+H)+.

Workup

  1. customplaced in a flame-dried flask under a nitrogen atmosphere
  2. temperatureThe mixture was heated
  3. temperatureto reflux
  4. temperatureas reflux
  5. temperaturewas maintained
  6. additionAfter complete addition
  7. temperaturethe reaction mixture was refluxed an additional two hours
  8. stirringStirring
  9. customthe layers were separated
  10. washThe aqueous layer was washed with an additional 30 mL portion of diethyl ether
  11. additionmade basic by addition of 50% aq. sodium hydroxide solution
  12. extractionThe basic aqueous mixture was then extracted with three 50 mL portions of dichloromethane
  13. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  14. concentrationconcentrated on a rotary evaporator

Sources & evidence

ORD record
ord-bce7f3572a214512881df5d8fd680e9e
Source dataset
uspto-grants-2006_05
Patent number
US07049330B2

Reaction notes

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