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