ETHYL 4-BROMOTHIAZOLE-2-CARBOXYLATE synthesis

Yield:959755-96-5 56%

Reaction Conditions:

Stage #1:2,4-dibromo-1,3-thiazole with isopropylmagnesium chloride in tetrahydrofuran at 0; for 0.166667 h;
Stage #2:ethyl cyanoformate in tetrahydrofuran at 0 - 20; for 0.25 h;

Steps:

Ethyl 4-bromothiazole-2-carboxylate (10a)²
To asolution of 2,4-dibromothiazole (640 mg, 2.63mmol) in THF (10.0 mL) at 0 °C was added iPrMgCl(2.0 M in THF, 1.5 mL) dropwise. The reaction mixture was stirred at 0 °C for 10 minutes, and ethyl cyanoformate (0.65 mL, 6.60 mmol) was added. The resulting solution was stirred for additional 15 minutes at room temperature and quenched with NH₄Cl solution. The mixture was extracted with H₂O/Ethylacetate. The combined organic fraction was washed with brine and dried overMgSO₄, concentrated under reduced pressure and purified by column chromatography on silica gel (hexane/ethyl acetate = 10:1) to afford the titlecompound 10a (349 mg, 56 %) as white solid: ¹H-NMR (400 MHz, CDCl₃) δ 7.52 (s, 1H), 4.42 (q, J = 7.12 Hz, 2H), 1.37 (t, J = 7.12 Hz, 3H). ¹³C-NMR (100MHz, CDCl₃) δ 159.0, 158.9, 127.5, 123.7, 63.1, 14.2.

References:

Vu, Hoang Nam;Kim, Ji Young;Hassan, Ahmed H.E.;Choi, Kihang;Park, Jong-Hyun;Park, Ki Duk;Lee, Jae Kyun;Pae, Ae Nim;Choo, Hyunah;Min, Sun-Joon;Cho, Yong Seo [Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,# 1,p. 140 - 144] Location in patent:supporting information

FullText