Carbon Dioxide → 2-(4-Chloro-phenyl)-4-(2-hydroxy-ethyl)-thiazole-5-carboxylic acid
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][CH:10]=[C:11]([CH2:13][CH2:14][OH:15])[N:12]=2)=[CH:4][CH:3]=1.[Li]CCCC.[C:21](=[O:23])=[O:22]>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:9][C:10]([C:21]([OH:23])=[O:22])=[C:11]([CH2:13][CH2:14][OH:15])[N:12]=2)=[CH:6][CH:7]=1Participants
Conditions
- Temperature
- -75 °C
Procedure
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]+.
Workup
- customEvacuate the chilled solution under vacuum
- customthe temperature<−70° C
- additionSlowly add the red-purple solution via cannula over 3.5 h to a flask
- additioncontaining −75° C
- customthe temperature<−60° C
- customto come to room temperature
- customQuench
- customthe reaction with 1 N HCl (3000 mL)
- temperaturecool to 16° C.
- customcollect the precipitate
- filtrationby filtration
- washRinse the solid with hexanes (1400 mL)
- customdry under vacuum
Sources & evidence
- ORD record
- ord-291e65a6500b4f97b8b8efc76c88b820
- Source dataset
- uspto-grants-2011_11
- Patent number
- US08049013B2
Reaction notes
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