反应详情

温度

0 °C

(2R,4R)-4-(tert-Butyl-dimethyl-silanyloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (1.54 g, 4.5 mmol) was dissolved in 50 mL diethyl ether under an Ar atmosphere, cooled in an ice water bath, added dry pyridine (1.4 mL, 17.8 mmol), followed by the dropwise addition of oxalyl chloride (0.58 mL, 6.7 mmol). Reaction was stirred at 0° C. for 1 hour, then at ambient temperature for 1 hour. Diluted reaction with 50 mL diethyl ether, filtered off solids and concentrated filtrates. Redissolved filtrate in 30 mL dry DCM under an Ar atmosphere, cooled in an ice water bath, added 1 mL dry pyridine followed by 4-bromo-2-fluoroaniline (0.85 g, 4.5 mmol). Stirred reaction at ambient temperature for 20 hours. Concentrated solution, redissolved in EtOAc (150 mL), washed with 10% citric acid (3×100 mL), water (2×100 mL), brine, dried with MgSO4, filtered and concentrated. Purified on a silica gel column eluting with an automated system with gradient of 0-60% EtOAc in hexanes over 40 minutes. Combined and concentrated pure fractions to yield title compound as a clear oil. (0.96 g, 42%) APCI (AP−): 515.1, 517.1 (M−H)−.

1. temperaturecooled in an ice water bath
2. customReaction
3. waitat ambient temperature for 1 hour
4. additionDiluted
5. filtrationfiltered off solids and concentrated filtrates
6. temperatureRedissolved filtrate in 30 mL dry DCM under an Ar atmosphere, cooled in an ice water bath
7. additionadded 1 mL dry pyridine
8. stirringStirred
9. customreaction at ambient temperature for 20 hours
10. washwashed with 10% citric acid (3×100 mL), water (2×100 mL), brine
11. dry with materialdried with MgSO4
12. filtrationfiltered
13. concentrationconcentrated
14. customPurified on a silica gel column
15. washeluting with an automated system with gradient of 0-60% EtOAc in hexanes over 40 minutes
16. concentrationconcentrated pure fractions