Sodium Chloride → Ethyl 2-chlorothiazole-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

2-Amino-thiazole-4-carboxylic acid ethyl ester hydrobromide (34.46 g, 0.137 mol) was basified with a saturated solution of NaHCO3 (aq) (300 mL) and extracted with EtOAc (8×300 mL). The combined organic layers were dried over Na2SO4, filtered and the solvent evaporated in vacuo to liberate the free base. To a well stirred suspension of the free base in 9M H2SO4 (aq) (500 mL) at 0° C. to −5° C., CuSO4 (63.34 g, 0.397 mol) and NaCl (30.39 g, 0.520 mol) were added, followed by the dropwise addition of a solution of NaNO2 (10.39 g, 0.151 mol) in H2O (150 mL), over 45 min. The mixture was maintained at 0° C. for 1 h then warmed to RT. After 1 h at RT the reaction mixture was diluted with H2O (2 L) and extracted with Et2O (3×300 mL). The combined organic layers were dried over Na2SO4, filtered and the solvent was evaporated in vacuo to yield the title compound as a pale yellow amorphous solid (sufficiently pure to be used directly in the next step). MS m/z: 192.0 (M+H). Calc'd. for C6H6ClNO2S-191.64.

Provenance & Evidence