3-[[4-(2-Pyridinyl)piperazinyl]methyl]cyclohexanone → 1-(3-Phenyl-cyclohex-3-enylmethyl)-4-pyridin-2-yl-piperazine

HRID 1034192Notes

Reaction equation

HRID 1034192 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]1[CH2:12][CH2:11][N:10]([CH2:13][CH:14]2[CH2:19][CH2:18][CH2:17][C:16](=O)[CH2:15]2)[CH2:9][CH2:8]1.[C:21]1([Li])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>O1CCCC1>[C:21]1([C:16]2[CH2:15][CH:14]([CH2:13][N:10]3[CH2:11][CH2:12][N:7]([C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=4)[CH2:8][CH2:9]3)[CH2:19][CH2:18][CH:17]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

4

Reactant 2

HCID 152943993-[[4-(2-Pyridinyl)piperazinyl]methyl]cyclohexanoneHCID 178506676HCID 178506676, compound

Product 1

HCID 97977331-(3-Phenyl-cyclohex-3-enylmethyl)-4-pyridin-2-yl-piperazine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5.14 g of 3-[[4-(2-pyridinyl)-piperazinyl]methyl]cyclohexanone (Example B) in 250 mL of tetrahydrofuran at 0° C. under nitrogen is added dropwise a solution of phenyllithium (23.5 mL, 2.0M in cyclohexane/diethyl ether, 70/30). The solution is stirred at 0° C. for 1 hour, quenched with dropwise addition of 250 mL of saturated potassium phosphate monobasic solution. The solvent is evaporated in vacuo, the residue is basified with concentrated ammonium hydroxide to a pH of 9 and extracted into chloroform. The chloroform extract is dried over magnesium sulfate and filtered. A solution of the filtrate in 250 mL of chloroform containing 14.5 mL of trifluoroacetic acid is stirred at room temperature under nitrogen for 12 hours. The solvent is evaporated in vacuo, the residue is dissolved into ethyl acetate (250 mL) and washed with 1N sodium hydroxide solution and brine (250 mL of each). The ethyl acetate extract is dried over magnesium sulfate, filtered, and concentrated. The crude product is purified by medium pressure chromatography (silica gel, 90% hexanes - 10% ethyl acetate) to give (±)-1-[(3-phenyl-3-cyclohexen-1-yl)methyl]-4-(2-pyridinyl)piperazine (Example 4) as an off-white solid; mp 96°-98° C. and (±)-1-[(3-phenyl-2-cyclohexen-1-yl)methyl]-4-(2-pyridinyl)piperazine (Example 4a) as an off-white solid; mp 78°-82° C.

Workup

  1. customquenched with dropwise addition of 250 mL of saturated potassium phosphate monobasic solution
  2. customThe solvent is evaporated in vacuo
  3. extractionextracted into chloroform
  4. extractionThe chloroform extract
  5. dry with materialis dried over magnesium sulfate
  6. filtrationfiltered
  7. stirringA solution of the filtrate in 250 mL of chloroform containing 14.5 mL of trifluoroacetic acid is stirred at room temperature under nitrogen for 12 hours
  8. customThe solvent is evaporated in vacuo
  9. dissolutionthe residue is dissolved into ethyl acetate (250 mL)
  10. washwashed with 1N sodium hydroxide solution and brine (250 mL of each)
  11. extractionThe ethyl acetate extract
  12. dry with materialis dried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe crude product is purified by medium pressure chromatography (silica gel, 90% hexanes - 10% ethyl acetate)

Sources & evidence

ORD record
ord-abc9854984cf43cba863ab96a9759fbb
Source dataset
uspto-grants-1994_05
Patent number
US05314896

Reaction notes

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