Sodium Chloride → Ethyl 2-chlorothiazole-4-carboxylate

Temperature

0 °C

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.

1. extractionextracted with EtOAc (8×300 mL)
2. dry with materialThe combined organic layers were dried over Na2SO4
3. filtrationfiltered
4. customthe solvent evaporated in vacuo
5. additionsuspension of the free base in 9M H2SO4 (aq) (500 mL) at 0° C. to −5° C.
6. temperaturethen warmed to RT
7. extractionextracted with Et2O (3×300 mL)
8. dry with materialThe combined organic layers were dried over Na2SO4
9. filtrationfiltered
10. customthe solvent was evaporated in vacuo

ORD record

ord-1918b8b2faf6429e87c44894c7611f84

Source dataset

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07196104B2