Ethyl 2-bromothiazole-4-carboxylate

White solid

To a solution of ethyl 2-aminothiazole-4-carboxylate (100 g, 581 mmol) and copper (II) bromide (195 g, 871 mmol) in acetonitrile (1000 ml) at 0 °C, tert-butylnitrite (104 ml, 871 mmol) was added dropwise. The reaction mixture was warmed to room temperature and stirred for 12h. After completion of thereaction, the reaction mixture was diluted with a mixture of ethyl acetate (1000 ml) and water (3000 ml) and then acidified to pH 2 using iN hydrochloric acid. The two layers were separated and the aqueous layer was again extracted three times with ethyl acetate (500 ml). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by recrystallization from hexane to obtain pure ethyl 2-bromo-1, 3-thiazole-4-carboxylate (115 g, 84percent yield).‘H-NMR (400 MHz, DMSO-d6) 8.52 (s, IH), 4.29 (q, J 7.1 Hz, 2H), 1.29 (t, J 7.1 Hz, 3H)MS: m/z235.90. [M+1].Step A Preparation of ethyl 2-bromothiazole-4-carboxylate (4)tert-Butyl nitrite (prepared from 0.61 mol of NaNO2 and 110 mL of tert-butyl alcohol)were added dropwise to a suspension of CuBr2 (260 g, 1.16 mol) and ethyl 2-aminothiazole-4-carboxylate (100 g, 0.58 mol) in ACN (500 mL) at 0 °C over a period of 1 hour. The mixture was stirred for 12 hours at room temperature, then quenched with EtOAc (800 mL) and water (800 mL). The mixture was filtered, and the filtrate was separated into aqueous and organic phase. The aqueous phase was extracted with EtOAc (800 mLx2). The combined organic extracts were washed with 5percent KHSO4 aqueous (300 mLx3), saturated aqueous NaHCO3 (300mLx3), and brine (300 mLx 1), dried (Na2SO4), and concentrated to dryness to give ethyl 2- bromothiazole-4-carboxylate (79.4g, 58percent yield) which was used in the next step without further purification. ‘H NMR (300 MHz, DMSO-d6): ö 7.45 (s, 1H), 4.20 (q, J=7.2 Hz, 2H), 1.25 (t, J7.2 Hz, 3H).In a round bottom flask, dimethyl sulfoxide was heated to 60 ° C, was added NaNO2 (7.1g, 102.3mmol) obtained in Step with the 2-aminothiazol-4-carboxylate (4.4g, 25.6 mmol), and stir until completely dissolved. 40percent HBr (20.7g, 102.3mmol)0.5h The round bottom flask was placed in an ice bath, was slowly added dropwise containing 40percent HBr (20.7g, 102.3mmol) dimethylsulfoxide solution, in an ice bath the reaction 0.5h. TLC monitoring. After completion of the reaction, ethyl acetate was added, followed by distilled water, the organic layer was washed with saturated brine. 2--4- Drying, filtration, and the filtrate evaporated under reduced pressure to give 2-bromo-thiazole-4-carboxylic acid ethyl ester crude. (:=1:1)1.9g32.0percent Column chromatography (ethyl acetate: petroleum ether = 1: 1) isolated, recrystallized from petroleum ether to give 1.9g, 32.0percent yield.

Molecular Weight:236.09
XLogP3:2.5
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:234.93026
Monoisotopic Mass:234.93026
Topological Polar Surface Area:67.4
Heavy Atom Count:11
Complexity:156
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes