Hydrochloric Acid → 5-Iodo-3-methyl-1,2-thiazole-4-carboxylic acid

Temperature

-78 °C

To a solution of 3-methylisothiazole-4-carboxylic acid (C-4) (3.9 g, 27.3 mmol) in anhydrous THF (150 mL) at −78° C. under argon, n-butyl lithium solution (27.3 mL, 68.3 mmol) is added dropwise and the resulting mixture is stirred at −78° C. for 1 h. To this mixture, a solution of iodine (13.9 g, 54.6 mmol) in THF (50 mL) is added slowly and the resulting mixture is stirred at RT for 1 h. The mixture is acidified with concentrated HCl to adjust the pH to 3-4, and then extracted with ethyl acetate. The organic layer is washed with aqueous Na2SO3 solution. The aqueous layer is extracted with ethyl acetate. The combined organic layers are washed with brine, dried over Na2SO4 and filtered. The filtrate is concentrated in vacuo to afford the product, 5-iodo-3-methylisothiazole-4-carboxylic acid (C-5).

1. stirringthe resulting mixture is stirred at RT for 1 h
2. extractionextracted with ethyl acetate
3. washThe organic layer is washed with aqueous Na2SO3 solution
4. extractionThe aqueous layer is extracted with ethyl acetate
5. washThe combined organic layers are washed with brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationThe filtrate is concentrated in vacuo

ORD record

ord-28328ec3d1244ff39be1feb0757abeeb

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09255108B2