Hydrochloric Acid → 4-Methoxymethyl-pyrrolidine-1,2-dicarboxylic acid 2-[2-(4-bromo-phenyl)-2-oxo-ethyl]ester 1-tert-butyl ester

4-Methoxymethyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (461 mg, 1.68 mmol) was dissolved in MeOH (17 mL) and LiOH (1 M in H2O, 8.5 mL, 8.5 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 (9 mL, 9 mmol) and extracted with DCM (3×). The combined organics were dried over MgSO4, filtered and concentrated. The residue was dissolved in MeCN (17 mL) and treated with 2,4′-dibromoacetophenone (514 mg, 1.85 mmol), and triethylamine (0.258 mL, 1.85 mmol). After stirring for 2 h, the solvent was removed and the solid was suspended in EtOAc. The organic layer was washed with saturated aqueous NaHCO3 and brine then dried over MgSO4, filtered and concentrated. The crude residue was purified by silica column chromatography (15% to 35% EtOAc/Hex) to afford the title compound (746 mg, 97%).

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 (17 mL)
8. stirringAfter stirring for 2 h
9. customthe solvent was removed
10. washThe organic layer was washed with saturated aqueous NaHCO3 and brine
11. dry with materialthen dried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated
14. customThe crude residue was purified by silica column chromatography (15% to 35% EtOAc/Hex)

ORD 기록

ord-447e37ce536c4d889bd3160fa4b2532e

출처 데이터셋

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08088368B2