反应详情

To a solution of tert-butyl (1R)-1-(hydroxymethyl)-3-[4-(trifluoromethyl)phenyl]propylcarbamate XXXVIII (41.3 g; 0.124 mol) in 60% aqueous acetone was added a solid sodium (meta)periodate (266 g; 1.24 mol) followed by ruthenium(II) oxide hydrate (1.65 g; 12.4 mmol). The greenish suspension was stirred for 3 h before adding propan-2-ol (500 mL) and stirring for an additional 30 min to consume excess oxidant. The resulting suspension was filtered through Celite, and the filtrate was concentrated under reduced vacuum to give a brown oil. To the brown foam was added 1 N HCl to pH=1 extracted with EtOAc. The organic layer was washed with brine and dried with MgSO4. The crude residue was then purified on a silica gel column (10:1 hexane:EtOAc) to obtain (2R)-2-[(tert-butoxycarbonyl)amino]-4-[4-(trifluoromethyl)phenyl]butanoic acid XXXIX (18 g; 51.8 mmol, 42% yield). 1H NMR (CDCl3) 1.46 (brs, 9H), 1.93-2.30 (m, 2H), 2.68-2.87 (m, 2H), 4.12-4.47 (m, 1H), 5.04-5.23 (m, 1H), 7.30 (d, J=8 Hz, 2H), 7.55 (d, J=8 Hz, 2H); ESIMS found for C16H20F3NO4 m/z 348.3 (M+H).

1. stirringstirring for an additional 30 min
2. customto consume excess oxidant
3. filtrationThe resulting suspension was filtered through Celite
4. concentrationthe filtrate was concentrated under reduced vacuum
5. customto give a brown oil
6. extractionextracted with EtOAc
7. washThe organic layer was washed with brine
8. dry with materialdried with MgSO4
9. customThe crude residue was then purified on a silica gel column (10:1 hexane:EtOAc)