Ethyl 2-chloro-5-Methyl-1,3-thiazole-4-carboxylate synthesis

Yield:-

Reaction Conditions:

with copper dichloride;sodium t-butanolate in acetonitrile at 80; for 16 h;Inert atmosphere;

Steps:

180.A Step A. Ethyl 2-chloro-5-methylthiazole-4-carboxylate
To a solution of t-BuONO (2.21 g, 21.5 mmol) and CuCl₂ (2.16 g, 16.1 mmol) in MeCN (30 mL) was added ethyl 2-amino-5- methylthiazole-4-carboxylate (2.0 g, 10.7 mmol). Then the mixture was stirred at 80 °C for 16 hours. The mixture was quenched with sat. aq. NH4Cl solution (30 mL). Then the mixture was poured into water (20 mL) and extracted with ethyl acetate (20 mL × 2). The combined organic phase was washed with brine (20 mL × 3), dried with anhydrous Na₂SO₄, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography (SiO2, gradient elution: 0 - 10% ethyl acetate in petroleum ether) to give the title compound as light yellow solid. MS (ESI): mass calcd. for C₇H₈ClNO₂S, 205.0; m/z found, 206.1 [M+H]⁺.¹H NMR (400MHz, CDCl₃) δ = 4.34 (q, J=7.2 Hz, 2H), 2.70 (s, 3H), 1.37 (t, J=7.2 Hz, 3H).

References:

JANSSEN BIOTECH, INC. WO2021/70132, 2021, A1 Location in patent:Page/Page column 200; 381-382