[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Cl)=[CH:4][CH:3]=1.C(O)C.[NH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1>CCOCC>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[CH:4][CH:3]=1A solution of 29 g of p-fluorobenzyl chloride in 50 g of reagent ethanol was added dropwise to a stirred solution of 34.5 g of piperazine in 150 g of reagent ethanol. A cold water bath was used to maintain the reaction temperature at 20° C. during the addition. The reaction mixture was stirred for an additional 11/2 hours and then added to 2 liters of ether. Precipitated piperazine hydrochloride was filtered off. The filtrate was concentrated to an oil, which was chromatographed on a silica column, the eluant being a mixture of CH2Cl2 /methanol/ammonium hydroxide in the ratio of 45:5:1. After concentration of appropriate fractions, 21.7 g of 1-(4-fluorobenzyl)piperazine were isolated as a colorless liquid (56% of theory).
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