反应详情

温度

50 °C

To a solution of [tert-butoxycarbonyl-(3-chloro-propyl)-amino]-(4-fluoro-phenyl)-acetic acid methyl ester (10.91 g) in acetonitrile (60 mL) was added benzyltriethylammoniumchloride (3.32 g) (see also Chemistry of Heterocyclic Compound, 36, 2000, 416-420) followed by solid potassium carbonate (12.1 g, finely ground). The reaction mixture was stirred at 50° C. for 20 hours. A further 1.6 g of benzyltriethylammoniumchloride and 4 g of potassium carbonate was added to push the reaction to completion. The reaction mixture was filtered and the filtrate was reduced in vacuo. The residue was diluted with water and extracted with chloroform (3×50 mL). The combined organic phases were washed with brine and dried over sodium sulfate. Filtration and evaporation of the volatiles in vacuo afforded a crude residue which was purified using flash column chromatography (EtOAc/Heptane 2:8) on silica gel to afford the desired 2-(4-Fluoro-phenyl)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (4.25, MS (ES+): 324.3 (MH+)) as a pale yellow oil.

1. customthe reaction to completion
2. filtrationThe reaction mixture was filtered
3. additionThe residue was diluted with water
4. extractionextracted with chloroform (3×50 mL)
5. washThe combined organic phases were washed with brine
6. dry with materialdried over sodium sulfate
7. filtrationFiltration and evaporation of the volatiles in vacuo
8. customafforded a crude residue which
9. customwas purified