Diisopropylamine → Ethyl 2,4-dibromothiazole-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

In a 50 mL 2-neck RBF equipped with septa, a solution of N,N-Diisopropylamine (0.04374 g, 0.4322 mmol) in tetrahydrofuran (1.33 mL, 16.4 mmol) under atmosphere of argon was cooled at −78° C., at which point n-butyllithium (2.50 M in hexane, 0.1647 mL, 0.4116 mmol) was added dropwise and the resulting solution was stirred for 30 minutes at −78° C. To the above solution was added dropwise a solution of 2,4-dibromothiazole (0.100 g, 0.412 mmol) in tetrahydrofuran (1.33 mL, 16.4 mmol) at −78° C., and this solution was stirred for 30 min −78° C. Next, ethyl chloroformate (0.07872 mL, 0.8233 mmol) was added dropwise at −78° C. and the mixture was stirred for 30 minutes. The reaction was quenched by addition of water (20 mL), the layers were separated, and the aqueous layer was extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified via silica gel column chromatography (12 g Analogix column, gradient elution 5% to 10% EtOAc in hexane) to afford ethyl 2,4-dibromo-1,3-thiazole-5-carboxylate (60 mg, yield 46%). LC/MS: (FA) ES+ 314, 316, 318; 1H NMR (400 MHz, CDCl3) δ 4.37 (q, J=7.1, 2H), 1.44-1.33 (m, 3H).

Provenance & Evidence