反应详情

温度

-75 °C

To a 500 mL 3-neck round bottom flask equipped with dropping funnel and internal temp monitor was added THF (200 mL) and N,N-Diisopropylamine (14.7 mL, 105 mmol) under atmosphere of Argon. After cooling at −75° C., 2.50 M of n-Butyllithium in Hexane (41.1 mL, 103 mmol) was added dropwise into the solution over 30 min. The internal temperature was kept below −70° C. and the resulting solution was stirred for 15 min at −75° C. To this LDA solution was added a solution of 2,4-dibromothiazole (25.0 g, 99.8 mmol) in THF (60 mL) via dropping funnel over 40 min and the internal temperature was kept below −70° C., then this solution was stirred for 20 min at −75° C. To this solution was added crushed dry ice at −75° C. and the mixture was stirred for 15 min. At that time, 10 mL water was added dropwise. Cooling bath was removed and the mixture was brought to r.t. over 1 hour with a water bath. The solvent was evaporated under reduced pressure to give a solid residue. The residue was suspended in 100 mL water, basified with 1.00 M of Sodium hydroxide in water (110 mL) and extracted with 100 mL ether. The ether layer was washed with 0.5 N NaOH (2×30 mL). The combined aqueous solution was acidified with conc. HCl with ice to pH˜2, extracted with ether (5×100 mL, adjusting pH˜2 each time after separation). The combined ether solution was washed with brine, dried over Na2SO4, filtered, evaporated to give a solid product (28.04 g, 98%). LCMS: (FA) ES+ 288, ES− 286.

1. customTo a 500 mL 3-neck round bottom flask equipped
2. customwas kept below −70° C.
3. customover 40 min
4. customwas kept below −70° C.
5. stirringthis solution was stirred for 20 min at −75° C
6. additionTo this solution was added
7. stirringthe mixture was stirred for 15 min
8. temperatureCooling bath
9. customwas removed
10. waitthe mixture was brought to r.t. over 1 hour with a water bath
11. customThe solvent was evaporated under reduced pressure
12. customto give a solid residue
13. extractionextracted with 100 mL ether
14. washThe ether layer was washed with 0.5 N NaOH (2×30 mL)
15. extractionextracted with ether (5×100 mL, adjusting pH˜2 each time after separation)
16. washThe combined ether solution was washed with brine
17. dry with materialdried over Na2SO4
18. filtrationfiltered
19. customevaporated