1017598-71-8

5326-23-8

3612-20-2

1017598-71-8

1. to a tetrahydrofuran solution (110 mL) of 2,2,6,6-tetramethylpiperidine (16.14 g, 113.10 mmol) was slowly added dropwise to a hexane solution (94 mL, 150.81 mmol) of 1.6 M n-butyllithium (94 mL, 150.81 mmol) at -78 °C and stirring was continued for 1 hr after completion of the dropwise addition. 2. 6-Chloronicotinic acid (6.0 g, 37.70 mmol) in tetrahydrofuran solution (50 mL) was added dropwise to the above reaction mixture over 1 hour and stirring was continued for 2 hours after completion of the dropwise addition. 3. at -78 °C, tetrahydrofuran solution (50 mL) of 1-benzyl-4-piperidone (21.6 g, 113.10 mmol) was added dropwise to the reaction mixture and stirring was continued for 2 hours after dropwise addition. 4. Water (70 mL) was added to the reaction mixture and then slowly warmed to room temperature. 5. The aqueous layer was separated and the organic layer was extracted with 1N aqueous sodium hydroxide solution (2 x 75mL). 6. the resulting aqueous layers were combined and extracted with ether (100 mL), followed by acidification of the aqueous layer to pH ≈ 1 by addition of concentrated hydrochloric acid. 7. After acidification with stirring for 1 h, the precipitate was collected by filtration, washed with water and then dissolved in ethyl acetate. 8. The organic layer was washed with saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate and subsequently concentrated under reduced pressure. 9. The residue was washed with ether to give the target product. The yield was 66% and mass spectral analysis showed m/z 329 [M+H]+ with a retention time of 0.72 min (LC-MS method Z012_S04).