Hydrochloric Acid → 5-Bromo-2-iodopyridin-3-ol

A 500 mL, one neck round bottom flask was charged with 5-bromopyridin-3-ol (10.00 g, 57.5 mmol), 80 mL water and a stirbar. The slurry was treated with sodium carbonate monohydrate crystals (4.80 ml, 115 mmol), and the flask was swept with Ar. After 15 minutes, the slurry was gently heated with a heat gun until the solution became homogenous. The solution was stirred for an additional 15 minutes, and iodine (mallinckrodt) (14.6 g, 57.5 mmol) was added. The reaction was stirred under Ar overnight in a dark hood. The slurry was then carefully treated with 2 N HCl until a pH of 2.5 was observed. The slurry was filtered, and the collected solids were washed with water (2×50 mL). The solids were dried under a stream of nitrogen for 3 h, dissolved in 100 mL hot MeOH, filtered hot, and allowed to cool over 96 h. The crystals that had formed over this time were collected using a pressure filter equipped with a 0.22 μm PTFE membrane. The solids were washed with MeOH (2×25 mL), and DCM (3×30 mL). The solids were dried under a stream of nitrogen for 2 h, and then at 60° C. and <1 mm Hg for 30 minutes to afford 5-bromo-2-iodopyridin-3-ol (7.9197 g, 45.9% yield). 1H NMR (400 MHz, THF) δ ppm 7.20 (dd, J=2.10, 0.44 Hz, 1H) 7.98 (dd, J=2.10, 0.44 Hz, 1H) 9.78 (s, 1H). 13C NMR (101 MHz, THF) δ ppm 109.16 (s, 1 C) 120.77 (s, 1 C) 124.01 (s, 1 C) 143.16 (s, 1 C) 155.87 (s, 1 C). HPLC-MS: retention time=1.69 min (98.6%@215 nm; 95.4% @254 nm; m/z=299.8, calculated for C5H3I79BrNO+H+=299.8; m/z=301.8, calculated for C5H3I81BrNO+H+=301.8).

1. temperaturethe slurry was gently heated with a heat gun until the solution
2. stirringThe reaction was stirred under Ar overnight in a dark hood
3. filtrationThe slurry was filtered
4. washthe collected solids were washed with water (2×50 mL)
5. customThe solids were dried under a stream of nitrogen for 3 h
6. dissolutiondissolved in 100 mL hot MeOH
7. filtrationfiltered hot
8. temperatureto cool over 96 h
9. customThe crystals that had formed over this time
10. customwere collected
11. filtrationfilter
12. customequipped with a 0.22 μm PTFE membrane
13. washThe solids were washed with MeOH (2×25 mL), and DCM (3×30 mL)
14. customThe solids were dried under a stream of nitrogen for 2 h

ORD record

ord-d2c686076db9438aba33a4b0f3f0396c

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07928140B2