tert-Butanol → tert-Butyl (6-bromo-4-iodopyridin-3-yl)carbamate

Temperature

110 °C

A mixture of 6-bromo-4-iodo-nicotinic acid (18.3 g, 55.7 mmol), diphenylphosphorylazide (18 mL, 83.6 mmol) and triethylamine (23.5 mL, 167.2 mmol) in tert-butanol (110 mL) and toluene (120 mL) was heated at 110° C. for 3 h. The mixture was allowed to cool to ambient temperature then evaporated under reduced pressure. The resultant oil was treated with water (150 mL) and extracted with ethyl acetate (2×300 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered and evaporated to give a black solid. The resultant black solid was triturated with methanol (75 mL), collected by filtration, then washed with diethyl ether (30 mL) and left to air dry to afford the title compound as a brown solid (7.5 g, 34%). The remaining filtrate was evaporated and purified by flash chromatography on a pad of silica. The pad was washed with 20% ethyl acetate in cyclohexane. Collecting all fractions containing product followed by evaporation in vacuo and trituation with cyclohexane afforded further title compound (8.9 g, 40%) as a white solid (combined yield—16.4 g, 74%). 1H NMR (CDCl3, 300 MHz): 8.95 (s, 1H), 7.87 (s, 1H), 6.64 (s, 1H), 1.54 (s, 9H). LCMS (Method B): RT=3.83 min, M+H+=399/401.

1. temperatureto cool to ambient temperature
2. customthen evaporated under reduced pressure
3. additionThe resultant oil was treated with water (150 mL)
4. extractionextracted with ethyl acetate (2×300 mL)
5. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
6. filtrationfiltered
7. customevaporated
8. customto give a black solid
9. customThe resultant black solid was triturated with methanol (75 mL)
10. filtrationcollected by filtration
11. washwashed with diethyl ether (30 mL)
12. waitleft to air
13. customdry

ORD record

ord-02cc8f47958844c29d699c80d0ffdbca

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216980B2