Carbon Dioxide → 2-(4-Chloro-phenyl)-4-(2-hydroxy-ethyl)-thiazole-5-carboxylic acid

Dissolve 2-[2-(4-chloro-phenyl)-thiazol-4-yl]-ethanol (107 g gross, 91 g net, 380 mmol) in THF (1210 mL) and cool to about −75° C. Evacuate the chilled solution under vacuum and fill with nitrogen three times. Slowly add n-BuLi (1.6 M in hexanes, 530 mL, 848 mmol) over approximately 4 h, keeping the temperature<−70° C. Slowly add the red-purple solution via cannula over 3.5 h to a flask containing −75° C. THF that has been saturated with CO2 gas (approximately 390 g) keeping the temperature<−60° C. Charge the resulting brown slurry with additional CO2 gas (approximately 355 g) and then allow the slurry to come to room temperature while stirring mechanically overnight. Quench the reaction with 1 N HCl (3000 mL), cool to 16° C., and collect the precipitate by filtration. Rinse the solid with hexanes (1400 mL) and dry under vacuum to give 81.3 g (75%) of the title compound. ES/MS m/z (35Cl) 284.0 [M+1]+.

1. customEvacuate the chilled solution under vacuum
2. customthe temperature<−70° C
3. additionSlowly add the red-purple solution via cannula over 3.5 h to a flask
4. additioncontaining −75° C
5. customthe temperature<−60° C
6. customto come to room temperature
7. customQuench
8. customthe reaction with 1 N HCl (3000 mL)
9. temperaturecool to 16° C.
10. customcollect the precipitate
11. filtrationby filtration
12. washRinse the solid with hexanes (1400 mL)
13. customdry under vacuum

ORD record

ord-291e65a6500b4f97b8b8efc76c88b820

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08049013B2