反应详情

The procedure of Example 19 was repeated to give 19 g of crude 1-cyano-3-(4-fluorophenacyl)piperidine, except that 5.4 g of cyanogen bromide, 10.0 g of 1-methyl-3-(4-fluorophenacyl)piperidine (Example 3), and 110 ml of benzene were employed and the addition was carried out at ambient temperature over a 45-minute period. The crude cyanopiperidine was hydrolyzed as described in Example 21, using as the hydrolysis mixture a solution consisting of 80 ml of glacial acetic acid, 40 ml of water, and 20 ml of concentrated hydrochloric acid; hydrolysis time was increased to 19 hours. The final residue was taken up in diethyl ether and combined with a solution of 2.6 g of maleic acid in 200 ml of diethyl ether. An oil separated which crystallized upon standing. The solid, 5.5 g, was recrystallized 3 times from acetone/diethyl ether to give 3-(4-fluorophenacyl)piperidine, maleate salt, mp 131°-132°. The following elemental analysis was obtained:

1. additionthe addition
2. waitwas carried out at ambient temperature over a 45-minute period
3. customhydrolysis time
4. temperaturewas increased to 19 hours
5. customAn oil separated which
6. customcrystallized
7. customThe solid, 5.5 g, was recrystallized 3 times from acetone/diethyl ether