反应详情

To a solution of (R)-tert-butyl 3-(pyrrolidine-1-carbonyl)piperidine-1-carboxylate (58.82 g, 208.3 mmol) in anhydrous dichloromethane (100 mL) was added hydrogen chloride in 1,4-dioxane (260 mL, 1040 mmol, 4M). The reaction mixture was stirred vigorously at room temperature for 1 h. The solvent was removed under reduced pressure and the residue was left standing overnight at room temperature. The residue was triturated with ether (250 mL). The ether was decanted and dichloromethane was added followed by sonication in a warm bath. The solvent was removed under reduced pressure and the resulting solid was placed under high vacuum at 40° C. for 1 h to afford (R)-piperidin-3-yl(pyrrolidin-1-yl)methanone hydrochloride (48.41 g). The material was used for the next step without further purification. 1H NMR (400 MHz, CD3OD) δ 1.75-2.05 (m, 8H) 3.04-3.17 (m, 2H) 3.19-3.28 (m, 3H) 3.35-3.66 (m, 4H); MS (ES+) (M+H) 183.3.

1. customThe solvent was removed under reduced pressure
2. waitthe residue was left
3. waitstanding overnight at room temperature
4. customThe residue was triturated with ether (250 mL)
5. customThe ether was decanted
6. additiondichloromethane was added
7. customfollowed by sonication in a warm bath
8. customThe solvent was removed under reduced pressure
9. waitthe resulting solid was placed under high vacuum at 40° C. for 1 h