反应 #1597025

反应方程式

5-Chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide

4-chloro-2-(2-chloro-4-nitrophenylcarbamoyl)phenyl pyrrolidine-1,2-dicarboxylate

Compound 26

4-chloro-2-(2-chloro-4-nitrophenylcarbamoyl)phenyl pyrrolidine-1,2-dicarboxylate

(S)-2-tert-butyl pyrrolidine-2-carboxylate

diisopropylethylamine

bis(trichloromethyl)carbonate

→

(S)-tert-butyl 1-(chlorocarbonyl)pyrrolidine-2-carboxylate

溶剂

ethyl acetate

pyridine

dichloromethane

dichloromethane

反应条件

后处理

1. 1
   洗涤The reaction mixture was washed with 1N aqueous HCl
2. 2
   干燥dried over magnesium sulfate
3. 3
   浓缩concentrated to an oil
4. 4
   workup.DISSOLUTIONThe residue was dissolved in chloroform (5.0 mL)
5. 5
   workup.STIRRINGThe reaction mixture was stirred at room temperature for 72 hours
6. 6
   其他partitioned between ethyl acetate and 1N aqueous HCl
7. 7
   干燥dried over magnesium sulfate
8. 8
   浓缩concentrated to a solid
9. 9
   其他The product was isolated
10. 10
    洗涤7 hexanes as elution solvent
11. 11
    其他The product was recrystallized from ethyl acetate/hexanes

实验过程

(S)-2-tert-butyl 1-(4-chloro-2-(2-chloro-4-nitrophenylcarbamoyl)phenyl pyrrolidine-1,2-dicarboxylate (Compound 26). (S)-tert-butyl 1-(chlorocarbonyl)pyrrolidine-2-carboxylate was prepared following the procedure disclosed in U.S. Pat. No. 4,866,087 to Greenlee et al with minor modification. A solution of 1.06 g (6.19 mmol) (S)-2-tert-butyl pyrrolidine-2-carboxylate and diisopropylethylamine (3.2 mL, 18.57 mmol) in dichloromethane (5.0 mL) was introduced dropwise into a solution of 1.84 g (6.19 mmol) bis(trichloromethyl)carbonate in dichloromethane (5.0 mL) at ice-bath temperature. The mixture was allowed to warm to room temperature and was stirred for one hour. The reaction mixture was washed with 1N aqueous HCl, dried over magnesium sulfate, and concentrated to an oil. The residue was dissolved in chloroform (5.0 mL) and added dropwise to a suspension of 5-Chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide (1.82 g, 5.57 mmol) in pyridine (25 mL) containing 20 mg 4-dimethylaminopyridine. The reaction mixture was stirred at room temperature for 72 hours, then partitioned between ethyl acetate and 1N aqueous HCl, dried over magnesium sulfate, and concentrated to a solid. The product was isolated using silica gel chromatography with 3 ethyl acetate: 7 hexanes as elution solvent. The product was recrystallized from ethyl acetate/hexanes. 1H NMR reveals the existence of approximately a 1:1 ratio of rotational isomers. 1H NMR (CDCl3): δ1.331 (s, 4.5H, tert-butyl ester), 1.369 (s, 4.5H, tert-butyl ester), 1.833 (m, 3H, pyrrolidine C4 methylene and pyrrolidine C3 syn-H), 2.181 (m, 1H, pyrrolidine C3 anti-H), 3.500 (m, 2H, pyrrolidine C5 methylene), 4.113 (m, 0.5H, pyrrolidine methine), 4.362 (m, 0.5H, pyrrolidine methine), 7.158 (d, J=9 Hz, 0.5H, H3), 7.334 (d, J=9 Hz, 0.5H, H3), 7.661 (m, 1H, H4), 7.762 (m, 1H, H6), 8.131 (m, 1H, H6′), 8.312 (m, 1H, H5′), 8.388 (m, 1H, H3′), 10.274 (s, 0.5H, NH), 10.347 (s, 0.5H, NH).

来源