Water → 1-[2-(4-Cyclopropylmethylpiperazin-1-yl)phenyl]-3,3,5,5-tetramethylcyclohexanol

HRID 32270

Reaction equation

HRID 32270 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH:15]2[CH2:17][CH2:16]2)[CH2:10][CH2:9]1.C([Li])CCC.[CH3:23][C:24]1([CH3:33])[CH2:29][C:28]([CH3:31])([CH3:30])[CH2:27][C:26](=[O:32])[CH2:25]1.O>O1CCCC1.C(OCC)(=O)C>[CH:15]1([CH2:14][N:11]2[CH2:12][CH2:13][N:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[C:26]3([OH:32])[CH2:25][C:24]([CH3:23])([CH3:33])[CH2:29][C:28]([CH3:31])([CH3:30])[CH2:27]3)[CH2:9][CH2:10]2)[CH2:17][CH2:16]1

Participants

7

Reactant 4

HCID 962WaterHCID 843993,3,5,5-TetramethylcyclohexanoneHCID 231428391-(2-Bromophenyl)-4-cyclopropylmethylpiperazineHCID 178418339Butyllithium

Product 1

HCID 113032171-[2-(4-Cyclopropylmethylpiperazin-1-yl)phenyl]-3,3,5,5-tetramethylcyclohexanolYield 87.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-(2-bromophenyl)-4-cyclopropylmethylpiperazine (700 mg, 2.37 mmol) produced in Example (108a) in anhydrous tetrahydrofuran (7 mL) was added dropwise n-butyllithium (1.60 M solution in hexane, 1.63 mL, 2.61 mmol) over a period of 3 minutes at an external temperature of −70° C. After stirring for 45 minutes under the same conditions, 3,3,5,5-tetramethylcyclohexanone (0.49 mL, 2.85 mmol) was added dropwise to the reaction mixture over a period of 4 minutes at an external temperature of −70° C. Stirring was continued for 15 minutes under the same conditions, and then for 18 hours and 30 minutes while warming until the external temperature reached room temperature. Water was added to the reaction mixture and extraction was performed with ethyl acetate. 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 silica gel column chromatography (ethyl acetate/heptane) to give 765 mg of the title compound as a light yellow oil.

Workup

  1. additionwas added dropwise to the reaction mixture over a period of 4 minutes at an external temperature of −70° C
  2. waitfor 18 hours
  3. temperature30 minutes while warming until the external temperature
  4. customreached room temperature
  5. washThe separated organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationThe desiccant was filtered off
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe resultant residue was purified by silica gel column chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-a2d3364cb9754b3db575067c3b9b3f39
Source dataset
uspto-grants-2008_09
Patent number
US07425554B2

Linked notes

Loading…