Iodine → (4-Iodo-pyridin-3-YL)-carbamic acid tert-butyl ester

Temperature

-78 °C

A solution of Example 17A (2.16 g, 11.12 mmol) in anhydrous tetrahydrofuran (50 mL) under N2 was cooled to −78° C. and treated dropwise with 1.7 M tert-butyl lithium in pentane (16.35 mL, 27.8 mmol). The mixture was stirred at −78° C. for 15 minutes, warmed to −30° C. and stirred for 2.5 hours. The dark brick-red solution was re-cooled to −78° C. and a solution of iodine (7.06 g, 27.8 mmol) in anhydrous tetrahydrofuran (18.5 mL) was added dropwise over 20 minutes to give a thick reaction mixture that was difficult to stir. The mixture was swirled at −78° C. for 15 minutes, warmed to −30° C., stirred for 40 minutes and warmed to 0° C. The mixture was quenched by addition of H2O (100 mL) and treated with solid Na2SO3 until a constant yellow color was achieved. The mixture was diluted with ethyl acetate and the layers were separated. The organic layer was washed with saturated sodium chloride solution, dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated by rotary evaporation. Purification by chromatography on silica eluting with 10%-20% ethyl acetate in dichloromethane afforded the title compound as an amber oil which crystallized upon standing (2.32 g, 65%). MS (DCI+) m/z 321 (M+H)+.

1. temperaturewarmed to −30° C.
2. stirringstirred for 2.5 hours
3. temperatureThe dark brick-red solution was re-cooled to −78° C.
4. customto give a thick reaction mixture that
5. stirringto stir
6. waitThe mixture was swirled at −78° C. for 15 minutes
7. temperaturewarmed to −30° C.
8. stirringstirred for 40 minutes
9. temperaturewarmed to 0° C
10. customThe mixture was quenched by addition of H2O (100 mL)
11. additiontreated with solid Na2SO3 until a constant yellow color
12. additionThe mixture was diluted with ethyl acetate
13. customthe layers were separated
14. washThe organic layer was washed with saturated sodium chloride solution
15. dry with materialdried over anhydrous Na2SO4
16. filtrationfiltered
17. concentrationthe filtrate was concentrated by rotary evaporation
18. customPurification by chromatography on silica eluting with 10%-20% ethyl acetate in dichloromethane

ORD record

ord-f24deb5cc23f48cebda7735ee3f8b5b2

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09173887B2