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To a stirred solution of 50 g (0.35 mol) of N-acetyl-4-piperidone and 31 g (0.35 mol) of morpholine in benzene (350 mL) was added a catalytic amount (˜0.25 g) of p-toluenesulfonic acid. The mixture was heated to reflux for 10 h with a Dean-Stark trap. The solvent was removed under reduced pressure to give a brown oil. The crude product was diluted with CH2Cl2 (175 mL) and 50.0 mL (0.35 mol) of Et3N was added. The mixture was cooled to 0° C. and a solution of 45.0 mL (0.35 mol) of 4-chlorobenzoyl chloride in CH2Cl2 (50 mL) was added slowly by dropping funnel over 1 h. The mixture was allowed to warm to room temperature and stirred overnight. The reaction was then diluted with 1 N HCl (150 mL) and stirred vigorously for 3 h. The aqueous layer was extracted with CH2Cl2 (3×250 mL) and the combined extracts were dried over Na2SO4 and the solvent was removed under reduced pressure. The crude oil was diluted with EtOH (350 mL) and cooled to 0° C. To this stirred solution was slowly added 33.0 mL (1.06 mol) of hydrazine and the mixture was allowed to warm to room temperature and stir overnight during which time a white precipitate formed. The volume of the reaction was reduced to ˜150 mL and EtOAc (750 mL) was added to the mixture. The suspension was stirred vigorously for 2 h and was filtered then washed with EtOAc (2×200 mL) and dried under vacuum to afford 41.4 g (42% over 3 steps) of a pale yellow solid. TLC (silica, 5% MeOH/CH2Cl2): Rf=0.3. MS (electrospray), m/z calculated for C14H14ClN3O [M+H]+ 276.08, observed 276.0. 1H NMR (400 MHz, CDCl3, a mixture of amide rotamers): 7.65 (d, J=8.4 Hz, 2H), 7.64 (d, J=9.3 Hz, 2H), 7.58 (d, J=10.5 Hz, 2H), 7.55 (d, J=8.5 Hz, 2H), 4.94 (s, 2H), 4.78 (s, 2H), 4.08 (t, J=5.9 Hz, 2H), 3.90 (t, J=5.8 Hz, 2H), 3.02 (t, J=5.8 Hz, 2H), 2.96 (t, J=5.9 Hz, 2H), 2.36 (s, 3H), 2.31 (s, 3H).

1. temperatureThe mixture was heated
2. temperatureto reflux for 10 h with a Dean-Stark trap
3. customThe solvent was removed under reduced pressure
4. customto give a brown oil
5. additionwas added
6. customover 1 h
7. temperatureto warm to room temperature
8. stirringstirred vigorously for 3 h
9. extractionThe aqueous layer was extracted with CH2Cl2 (3×250 mL)
10. dry with materialthe combined extracts were dried over Na2SO4
11. customthe solvent was removed under reduced pressure
12. additionThe crude oil was diluted with EtOH (350 mL)
13. temperaturecooled to 0° C
14. temperatureto warm to room temperature
15. stirringstir overnight during which time a white precipitate
16. customformed
17. additionwas added to the mixture
18. stirringThe suspension was stirred vigorously for 2 h
19. filtrationwas filtered
20. washthen washed with EtOAc (2×200 mL)
21. customdried under vacuum
22. customto afford 41.4 g (42% over 3 steps) of a pale yellow solid