反应详情

4-Difluoromethoxymethyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (398 mg, 1.29 mmol) was dissolved in MeOH (8 mL) and LiOH (1 M in H2O, 2 mL, 2 mmol) was added. After stirring at RT for 5 h, the MeOH was removed under reduced pressure. The aqueous solution was poured into a separatory funnel, diluted with 1 M HCl (2 mL, 2 mmol) and extracted with DCM (3×). The combined organics were dried over MgSO4, filtered and concentrated. The residue was dissolved in MeCN (4 mL) and treated with 2,4′-dibromoacetophenone (200 mg, 0.719 mmol), and triethylamine (0.100 mL, 0.719 mmol). After stirring for 15 h, the solvent was removed. The crude residue was purified by silica column chromatography (10% to 35% EtOAc/Hex) to afford the title compound (303 mg, 94%).

1. customthe MeOH was removed under reduced pressure
2. additionThe aqueous solution was poured into a separatory funnel
3. extractionextracted with DCM (3×)
4. dry with materialThe combined organics were dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. dissolutionThe residue was dissolved in MeCN (4 mL)
8. stirringAfter stirring for 15 h
9. customthe solvent was removed
10. customThe crude residue was purified by silica column chromatography (10% to 35% EtOAc/Hex)