
5-BROMOTHIAZOLE-2-CARBOXYLIC ACID synthesis
- Product Name:5-BROMOTHIAZOLE-2-CARBOXYLIC ACID
- CAS Number:957346-62-2
- Molecular formula:C4H2BrNO2S
- Molecular Weight:208.03

14190-59-1

957346-62-2
The general procedure for the synthesis of 5-bromothiazole-2-carboxylic acid from thiazole-2-carboxylic acid was as follows: thiazole-2-carboxylic acid (1.60 g, 12.4 mmol) was slowly added to dry tetrahydrofuran (THF, 100 mL) in a lithium diisopropylammonium (LDA, 1 M solution of THF/heptane/ethylbenzene, 26.0 mmol, 26 mL) solution. The reaction mixture was stirred at this temperature for 30 min. Subsequently, carbon tetrabromide (CBr4, 4.52 g, 13.6 mmol) was added and the reaction continued to be stirred for 2 hours. Upon completion of the reaction, the reaction was quenched by the addition of water (30 mL). After the mixture was brought to room temperature, it was diluted with saturated sodium bicarbonate (NaHCO3) aqueous solution (50 mL). The mixture was filtered through a diatomaceous earth pad and extracted with ethyl acetate (EtOAc, 50 mL). The organic layer was discarded and the aqueous layer was acidified with 1 M hydrochloric acid (HCl) to an acidic pH. The acidified aqueous solution was extracted with ethyl acetate (3 x 30 mL). The organic layers were combined, dried over anhydrous sodium sulfate (Na2SO4), and concentrated in vacuum to give 5-bromothiazole-2-carboxylic acid (0.42 g, 2.0 mmol, 16% yield).LCMS analysis: [M + H]+ = 207.90, measured value 208.0.

14190-59-1
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$15.00/1g

957346-62-2
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$75.00/100mg
Yield: 16%
Reaction Conditions:
Stage #1:1,3-thiazole-2-carboxylic acid with lithium diisopropyl amide in tetrahydrofuran;n-heptane;ethylbenzene at -78; for 0.5 h;
Stage #2: with carbon tetrabromide in tetrahydrofuran;n-heptane;ethylbenzene for 2 h;
Steps:
18.i
i) Thiazole-2-carboxylic acid (1.60 g, 12.4 mmol) was added to a solution of lithium diisopropylamine (1 M in THF/heptane/ethylbenzene, 26 mmol, 26 mL) in dry THE (100 mL) at -78 °C and the RM was stirred for 30 mi Tetrabromomethane (4.52 g, 13.6 mmol) was added and the RM was stirred for 2 h. The reactionRM was quenched by adding water (30 mL). The RM was allowed to reach RT and diluted by adding an aqueous saturated solution of NaHCO3 (50 mL). The RM was filtered through a pad of celite and extracted with EtOAc (50 mL). The organic layer was discarded and the aqueous layer acidified using a 1 N solution of HCI until pH 3-4. The solution was then extracted with EtOAc (3x 30 mL). The combined organic layer was dried over Na2SO4 and concentrated in vacuo to leave INT-18A (0.420 g, 2.02 mmol,16%). LCMS: caic. for [M+H]*=207.90, found 208.0.
References:
GRÜNENTHAL GMBH;NARDI, Antonio;RATCLIFFE, Paul;CRAAN, Tobias;HERTRAMPF, Thorsten;LESCH, Bernhard;KIME, Robert;STEINHAGEN, Henning WO2015/161928, 2015, A1 Location in patent:Page/Page column 36; 53; 54