反应详情

1-Methyl-3-piperidylmethylmagnesium chloride was prepared essentially as described in Example 1 from 30.5 g of 1-methyl-3-chloromethylpiperidine. Sufficient tetrahydrofuran was employed to provide a final solution volume of 305 ml. To 114 ml of this final solution of 1-methyl-3-piperidylmethylmagnesium chloride was added 8.9 g of benzonitrile dissolved in about 30 ml of tetrahydrofuran and the resulting solution was heated at reflux for 30 minutes. The reaction solution was cooled and added to 100 ml of water to which 4.5 g of ammonium chloride had been added. A tetrahydrofuran layer separated from the aqueous phase which was extracted with two 75-ml portions of diethyl ether. The resulting extracts and the tetrahydrofuran layer were combined and the resulting organic solution was washed with two 25-ml portions of water and extracted with three 75-ml portions of 3 N hydrochloric acid. The acid extracts were combined and washed with diethyl ether, heated to distill residual diethyl ether and tetrahydrofuran, then heated at reflux for 45 minutes. The resulting hydrochloric acid solution was cooled and made strongly alkaline with 3 N sodium hydroxide. The alkaline solution was extracted with three 100-ml portions of diethyl ether. The extracts were combined, washed with water, dried over anhydrous magnesium sulfate, and filtered. The diethyl ether solution was concentrated under reduced pressure and the residue was vacuum distilled to give 10.7 g of 1-methyl-3-phenacylpiperidine, bp 104°-114°/0.9 mm (collected as three fractions). The infrared and nuclear magnetic resonance spectra of the product were consistent with the assigned structure. The elemental analysis of the second fraction was as follows:

1. temperaturethe resulting solution was heated
2. temperatureat reflux for 30 minutes
3. temperatureThe reaction solution was cooled
4. additionhad been added
5. customA tetrahydrofuran layer separated from the aqueous phase which
6. extractionwas extracted with two 75-ml portions of diethyl ether
7. washthe resulting organic solution was washed with two 25-ml portions of water
8. extractionextracted with three 75-ml portions of 3 N hydrochloric acid
9. washwashed with diethyl ether
10. temperatureheated
11. distillationto distill residual diethyl ether and tetrahydrofuran
12. temperatureheated
13. temperatureat reflux for 45 minutes
14. temperatureThe resulting hydrochloric acid solution was cooled
15. extractionThe alkaline solution was extracted with three 100-ml portions of diethyl ether
16. washwashed with water
17. dry with materialdried over anhydrous magnesium sulfate
18. filtrationfiltered
19. concentrationThe diethyl ether solution was concentrated under reduced pressure
20. distillationdistilled
21. customto give
22. custom10.7 g of 1-methyl-3-phenacylpiperidine, bp 104°-114°/0.9 mm (collected as three fractions)