Hydrochloric Acid → [6-Chloro-4-iodo-5-(2,2,2-trifluoro-ethoxy)-pyridin-2-yl]-methanol

6-Chloro-5-hydroxy-4-iodo-2-pyridinemethanol (CAS Registry No. 208519-37-3) (21.5 g, 75 mmol) was dissolved in hexamethylphosphoramide (210 mL). Over a period of 30 min sodium hydride (3.0 g of 60% dispersion in oil, ˜75 mmol) was added with stirring at room temperature. The mixture was stirred for another 45 min at room temperature and 2,2,2-trifluoroethyl trifluoromethane sulfonate (12.5 mL, 90 mmol) was added drop wise with stirring and temperature control (<40° C.). The mixture was stirred for 18 h at 120° C., cooled to room temperature and poured into water (800 mL). The mixture was acidified with 2N—HCl (50 mL) and extracted with ethyl acetate (2×350 mL). Organic phases were washed with water (2×400 mL), pooled and dried with Na2SO4. Solvents were evaporated and the brown, solid residue (27.9 g) was purified by chromatography on silica with ethyl acetate/n-heptane (1:1) to give the title compound as a white solid (24.8 g, 90%), LC-MS (UV peak area/ESI) 100%, 367.916 (M+H)+.

1. stirringThe mixture was stirred for another 45 min at room temperature
2. stirringwith stirring
3. customtemperature control (<40° C.)
4. stirringThe mixture was stirred for 18 h at 120° C.
5. temperaturecooled to room temperature
6. extractionextracted with ethyl acetate (2×350 mL)
7. washOrganic phases were washed with water (2×400 mL)
8. dry with materialdried with Na2SO4
9. customSolvents were evaporated
10. customthe brown, solid residue (27.9 g) was purified by chromatography on silica with ethyl acetate/n-heptane (1:1)

ORDレコード

ord-3ded6d2ff14b4e8aaede9c1cb73701b6

出典データセット

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08729105B2