Acetic Anhydride → HCID 90402444, compound

Temperature

110 °C

5-bromo-6-chloro-3-iodopyridin-2-ol (12.9 g, 38.6 mmol) was suspended in acetic anhydride (40 mL, 420 mmol) and heated to 110° C. The mixture was heated at this temp for 1 h. After 1 h the reaction mixture appeared as a homogeneous solution. TLC (observed M+H mass in LCMS is primarily of des-OAc) indicated complete reaction. The solution was concentrated azeotroping with toluene (3×25 mL) to give 5-bromo-6-chloro-3-iodopyridin-2-yl acetate (14.5 g, 38.5 mmol, 100% yield) as a tan solid. The solid was taken onto the subsequent Sonogashira coupling without further purification. Observed LCMS reveals mostly hydrolysis product (starting material), but desired mass is present. LCMS: m/e 377 (M+H)+ LCMS retention time: 2.71 min. (Column: Phenomenex-Luna 50×2.0 mm 3u. Solvent A=90% Water: 10% Methanol: 0.1% TFA. Solvent B=10% Water: 90% Methanol: 0.1% TFA. Start % B=0. Final % B=100. Gradient Time=3 min. Flow Rate=0.8 mL/min.). 1H NMR (500 MHz, CDCl3) δ ppm 8.37 (s, 1H), 2.38 (s, 3H).

1. temperatureThe mixture was heated at this temp for 1 h
2. customreaction
3. concentrationThe solution was concentrated
4. customazeotroping with toluene (3×25 mL)

ORD record

ord-fcd03895ebb9413ebde2793319f02e96

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08962651B2