反应详情

温度

10 °C

A solution of N-tert-Butoxycarbonyl-4-piperidylacetaldehyde (4.5 grams, 19.8 mmol, from Step A), and morpholine (1.7 mL, 19.8 mmol) in 100 mL benzene was refluxed using a dean-stark apparatus. After refluxing over night the mixture was concentrated to provide the examine. The crude examine was dissolved in 40 mL DCM and the solution was cooled to 10° C. Propionyl chloride (1.7 mL, 19.8 mmol) and then triethylamine (1.4 mL, 9.9 mmol) were added. The mixture was gradually warmed to room temperature and stirred for 40 h then concentrated. The residue was dissolved in 60 mL of ethanol and hydrazine (6.2 mL, 198 mmol) was added. The solution was refluxed for 5 h. The solvent was removed and ethyl acetate was added. The organic was washed with water and sat'd sodium chloride then dried over magnesium sulfate and concentrated. Flash chromatography (0.5% MeOH/DCM →2% MeOH/DCM) afforded the title compound. 1H NMR (400 MHz, CDCl3): δ1.25-1.31 (t, 3H), 1.44-1.57 (m, 1H), 1.46 (s, 9H), 1.78-1.83 (s, 2H), 2.53-2.6 (m, 1H), 2.62-2.7 (q, 2H), 2.77-2.82 (m, 2H), 4.12-4.23 (m, 2H), 7.32 (s, 1H).

1. temperatureAfter refluxing over night the mixture
2. concentrationwas concentrated
3. customto provide the
4. temperatureThe mixture was gradually warmed to room temperature
5. concentrationthen concentrated
6. dissolutionThe residue was dissolved in 60 mL of ethanol
7. temperatureThe solution was refluxed for 5 h
8. customThe solvent was removed
9. additionethyl acetate was added
10. washThe organic was washed with water
11. dry with materialthen dried over magnesium sulfate
12. concentrationconcentrated