Hydrochloric Acid → cis-4-[3-(4,4-Dimethylcyclohexyl)-4-piperazin-1-ylphenyl]-2,6-dimethylmorpholine

HRID 32179Notes

Reaction equation

HRID 32179 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:25][C@H:24]([CH3:26])[O:23][C@H:22]([CH3:27])[CH2:21]3)=[CH:16][C:15]=2[CH:28]2[CH2:33][CH2:32][C:31]([CH3:35])([CH3:34])[CH2:30][CH2:29]2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(OCC)(=O)C.Cl.C(=O)([O-])[O-].[Na+].[Na+]>O.ClCCl>[CH3:34][C:31]1([CH3:35])[CH2:30][CH2:29][CH:28]([C:15]2[CH:16]=[C:17]([N:20]3[CH2:25][C@H:24]([CH3:26])[O:23][C@H:22]([CH3:27])[CH2:21]3)[CH:18]=[CH:19][C:14]=2[N:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)[CH2:33][CH2:32]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl Acetate2×HCID 10340Sodium CarbonateHCID 59769395cis-4-[2-(4,4-Dimethylcyclohexyl)-4-(2,6-dimethylmorpholin-4-yl)phenyl]piperazine-1-carboxylic acid t-butyl ester

Product 1

HCID 59769447cis-4-[3-(4,4-Dimethylcyclohexyl)-4-piperazin-1-ylphenyl]-2,6-dimethylmorpholineYield 87.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To cis-4-[2-(4,4-dimethylcyclohexyl)-4-(2,6-dimethylmorpholin-4-yl)phenyl]piperazine-1-carboxylic acid t-butyl ester (648 mg, 1.33 mmol) produced in Example (61a) was added a mixed solvent of ethyl acetate (5 mL)-dichloromethane (1 mL), followed by stirring at room temperature under a nitrogen atmosphere. A 4N solution of hydrogen chloride in ethyl acetate (5 mL, 20 mmol) was added dropwise thereto, followed by stirring for 17 hours under the same conditions. Saturated aqueous solution of sodium carbonate was added to the reaction mixture to make the mixture basic. Dichloromethane and water were added thereto and extraction was performed with dichloromethane. The separated organic layer was washed with brine and then dried over anhydrous sodium sulfate. The desiccant was filtered off and the filtrate was concentrated under reduced pressure. The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/hexane) to give 451 mg of the title compound as light yellow crystals.

Workup

  1. stirringby stirring for 17 hours under the same conditions
  2. extractionextraction
  3. washThe separated organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationThe desiccant was filtered off
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe resultant residue was purified by NH silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-b4491b63cd5a4966afbfd8c844b8a0d4
Source dataset
uspto-grants-2008_09
Patent number
US07425554B2

Reaction notes

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