反应详情

温度

25 °C

To 1-Benzyl-pyrrolidine-2-carboxylic acid (474) (Belokon, Y. N. at al; Tetrahedron Asymmetry 1998, 9, 4249-4252) in CH2Cl2 (20 mL) was added 2,2-dimethoxy-ethylamine (614 mg, 5.84 mmol), EDCl (1.12 g, 5.84 mmol), HOBT (658 mg, 4.87 mmol), and NMM (1.08 mL, 9.8 mmol). The reaction mixture was stirred overnight at 25° C. Saturated aqueous NaHCO3 solution (50 mL) was added. The aqueous layer was extracted with CH2Cl2 (50 mL×3). The combined organic layers was washed with brine (50 mL), dried over Na2SO4, and concentrated by rotary evaporator to give 1-benzyl-pyrrolidine-2-carboxylic acid (2,2-dimethoxy-ethyl)-amide as yellow oil. To 1-benzyl-pyrrolidine-2-carboxylic acid (2,2-dimethoxy-ethyl)-amide was added acetic acid (10 mL) and ammonium acetate (11 g). The reaction mixture was heated to 140° C. overnight. After it was cooled down, it was poured into 100 mL ice-water with stirring. Solid NaHCO3 was added in small portion with stirring to adjust the pH of the solution to 8-9. The aqueous solution was extracted with EtOAc (100 mL×2). The combined organic layers was washed with brine, dried over Na2SO4, and concentrated with rotary evaporator. Compound 475 (110 mg) was isolated by SiO2 chromatography (CH2Cl2/MeOH/NH3: 40:1:0.1 to 20:1:0.1). MS: m/z 228.3 [M+H]+.

1. extractionThe aqueous layer was extracted with CH2Cl2 (50 mL×3)
2. washThe combined organic layers was washed with brine (50 mL)
3. dry with materialdried over Na2SO4
4. concentrationconcentrated by rotary evaporator