Carbon Dioxide → 2,4-Dibromo-1,3-thiazole-5-carboxylic acid

Temperature

-75 °C

To a 500 mL 3-neck round bottom flask equipped with dropping funnel and internal temperature 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. The cooling bath was removed and the mixture was brought to rt over 1 h 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 to ˜pH 2, extracted with ether (5×100 mL, adjusting the pH to ˜2 each time after separation). The combined ether solutions were 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. customThe cooling bath was removed
9. waitthe mixture was brought to rt over 1 h with a water bath
10. customThe solvent was evaporated under reduced pressure
11. customto give a solid residue
12. extractionextracted with 100 mL ether
13. washThe ether layer was washed with 0.5 N NaOH (2×30 mL)
14. extractionextracted with ether (5×100 mL
15. customafter separation)
16. washThe combined ether solutions were washed with brine
17. dry with materialdried over Na2SO4
18. filtrationfiltered
19. customevaporated

ORD record

ord-4c6680588e6746518496e013bb309fa2

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796268B2