反应详情

(S)-3-((S)-2-Benzyloxy-1-hydroxyethyl)-pyrrolidine-1-carboxylic acid t-butyl ester (4.6 g, 14 mmol, 10. eq.) was combined with 4-fluorobenzotrifluoride (5.5 mL, 42.9 mmol, 3.0 eq.) in DMF (30 mL, 400 mmol). The mixture was degassed under nitrogen, and NaH (481 mg, 20.0 mmol) was added in small portions. The resulting mixture was stirred for 10 minutes at room temperature, followed by stirring at 90° C. for 3 hours. The mixture was then cooled to room temperature, extracted with hexanes (50 mL), and washed with water (50 mL) then 2M aqueous NaCl (50 mL). The organic layer was collected, stirred in activated carbon (460 mg) for 5 minutes, dried over Na2SO4, filtered, and concentrated. The resulting crude oil was dissolved in MeOH (50 mL), and 10% Pd/C (0.1:0.9, Palladium:carbon black, 670 mg, 630 μmol) was added under nitrogen. The mixture was stirred under hydrogen (1 atm) overnight. The mixture was filtered and the filtrate was concentrated. The resulting crude oil was dissolved in hexanes (˜30 mL) and EtOAc (˜15 ml), then concentrated until precipitate formed. Additional hexanes was added and the precipitate was stirred for 15 minutes. The precipitate was filtered and dried to give the title compound as a white solid (3.3 g).

1. customThe mixture was degassed under nitrogen
2. stirringby stirring at 90° C. for 3 hours
3. temperatureThe mixture was then cooled to room temperature
4. extractionextracted with hexanes (50 mL)
5. washwashed with water (50 mL)
6. customThe organic layer was collected
7. stirringstirred in activated carbon (460 mg) for 5 minutes
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. dissolutionThe resulting crude oil was dissolved in MeOH (50 mL)
12. stirringThe mixture was stirred under hydrogen (1 atm) overnight
13. filtrationThe mixture was filtered
14. concentrationthe filtrate was concentrated
15. dissolutionThe resulting crude oil was dissolved in hexanes (˜30 mL)
16. concentrationEtOAc (˜15 ml), then concentrated until precipitate
17. customformed
18. stirringthe precipitate was stirred for 15 minutes
19. filtrationThe precipitate was filtered
20. customdried