反应详情

To a stirred solution of tert-butyl 4-aminopiperidine-1-carboxylate (2.4 g, 12 mmol) in CH2Cl2 (30 mL) was added trimethylaluminum (6.0 mL, 12 mmol) dropwise. The resulting mixture was stirred for 15 minutes, then (S)-3-(4-bromo-2-fluoro-5-methylphenoxy)dihydrofuran-2(3H)-one (2.9 g, 10 mmol) in CH2Cl2 (30 mL) was added slowly and stirred at ambient temperature for 1 hour. The reaction was slowly quenched with 5% tartaric acid, neutralized with aqueous NaHCO3 and filtered through celite. The filtrate was extracted with CH2Cl2, dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel (100% EtOAc) to afford (S)-tert-butyl 4-(2-(4-bromo-2-fluoro-5-methylphenoxy)-4-hydroxybutanamido)piperidine-1-carboxylate (3.2 g, 6.5 mmol, 65% yield).

1. stirringstirred at ambient temperature for 1 hour
2. customThe reaction was slowly quenched with 5% tartaric acid
3. filtrationfiltered through celite
4. extractionThe filtrate was extracted with CH2Cl2
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified over silica gel (100% EtOAc)