反应详情

温度

0 °C

Pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (1.6 g, 7.4 mmol) was dissolved in 40 mL dry diethyl ether under Ar. The solution was cooled in an ice water bath as dry pyridine (3 mL, 37.2 mmol) was added, followed by the dropwise addition of oxalyl chloride (1.6 mL, 18.6 mmol). A precipitate formed immediately. The reaction was stirred vigorously at 0° C. for one hour, then at ambient temperature for one hour. 50 mL diethyl ether were added, and the mixture was filtered. The filtered off solids were washed with diethyl ether. The filtrates were combined and concentrated to give an off-white oil. The oil was redissolved in 40 mL dry DCM under Ar, cooled to 0° C., and 3 mL of pyridine were added, followed by 4′-amino-3′-fluoro-biphenyl-2-sulfonic acid tert-butylamide (2 g, 6.2 mmol). The reaction was allowed to warm to ambient temperature, stirred for 3 hours then concentrated. The concentrate was redissolved in 250 mL EtOAc, washed with 10% citric acid (2×100 mL), water (3×100 mL), brine (100 mL), dried with MgSO4, filtered and concentrated. The concentrate was purified on a silica gel column eluted with 30% moving to 50% EtOAc in hexanes. Combined and concentrated pure fractions to yield title compound as a white solid. (1.4 g, 42%) APCI (AP−): 518.2 (M−H)−.

1. additionwas added
2. customA precipitate formed immediately
3. waitat ambient temperature for one hour
4. filtrationthe mixture was filtered
5. filtrationThe filtered off solids
6. washwere washed with diethyl ether
7. concentrationconcentrated
8. customto give an off-white oil
9. temperaturecooled to 0° C.
10. temperatureto warm to ambient temperature
11. stirringstirred for 3 hours
12. concentrationthen concentrated
13. dissolutionThe concentrate was redissolved in 250 mL EtOAc
14. washwashed with 10% citric acid (2×100 mL), water (3×100 mL), brine (100 mL)
15. dry with materialdried with MgSO4
16. filtrationfiltered
17. concentrationconcentrated
18. customThe concentrate was purified on a silica gel column
19. washeluted with 30%
20. concentrationconcentrated pure fractions