反应详情

To a solution containing (2R)-N-[(2S)-2-hydroxy-3-phenoxypropyl]-6-iodo-3,4-dihydro-2H-chromene-2-carboxamide (Example 79, 9.204 mmol, 1 eq.) in THF (140 mL) at room temperature was slowly added borane-methyl sulfide complex (2 M in THF, 46.07 mmol, 5.0 eq.). After completion of addition, reaction solution was heated to reflux, maintained at that temperature for 2 hours, and then cooled to room temperature. The resulting solution was quenched with EtOH (5 mL) dropwise, then with 2 M HCl (20 mL) slowly. The resulting mixture was heated at reflux for 1 hour and was then allowed to cool to room temperature. This solution was basified with 1 N NaOH and extracted with ethyl acetate. The organic extract was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The resulting residue was dissolved in MeOH and EtOAc and filtered. The filtrate was concentrated and dried in vacuo to afford the product as a white solid in 99% yield. MH+=440.2, retention time (LC-MS)=2.24 min.

1. additionAfter completion of addition, reaction solution
2. temperaturewas heated
3. temperatureto reflux
4. temperaturemaintained at that temperature for 2 hours
5. customThe resulting solution was quenched with EtOH (5 mL) dropwise
6. temperatureThe resulting mixture was heated
7. temperatureat reflux for 1 hour
8. temperatureto cool to room temperature
9. extractionextracted with ethyl acetate
10. extractionThe organic extract
11. washwas washed with brine
12. dry with materialdried over anhydrous sodium sulfate
13. concentrationconcentrated in vacuo
14. dissolutionThe resulting residue was dissolved in MeOH
15. filtrationEtOAc and filtered
16. concentrationThe filtrate was concentrated
17. customdried in vacuo