Iodine → HCID 67467642, compound

Temperature

-78 °C

To a cold (−78° C.) solution of the triazole from preparation 59 (3.0 g, 12.4 mmol) in tetrahydrofuran (70 mL), under an atmosphere of nitrogen, was added n-butyllithium (2.5M in hexane, 5.5 ml, 14 mmol, 1.1 eq.) at such a rate as to maintain the temperature below −70° C. The resulting yellow solution was stirred at −78° C. for 2 hr before adding a solution of iodine (3.47 g, 13.7 mmol, 1.1 eq.) in tetrahydrofuran (10 mL). The resulting mixture was allowed to slowly warm to room temperature over 2 hr before concentrating the mixture by evaporation under reduced pressure. The residue was partition between tert-butyl methyl ether (150 mL) and a mixture of aqueous sodium hydrogen carbonate (1M, 50 mL) and aqueous sodium sulphite (1M, 100 ml). The organic phase was washed with saturated brine (20 mL) and dried over sodium sulphate. The resulting mixture was filtered and the filtrate concentrated under reduced pressure to give an orange solid. The crude solid was purified by chromatography on silica gel (100 g) eluting with a gradient of ethyl acetate in heptane (10:90 to 50:50) to give the title compound as a white solid (1.6 g, 55%).

1. temperatureto maintain the temperature below −70° C
2. temperatureto slowly warm to room temperature over 2 hr
3. concentrationbefore concentrating the mixture
4. customby evaporation under reduced pressure
5. customThe residue was partition between tert-butyl methyl ether (150 mL)
6. additiona mixture of aqueous sodium hydrogen carbonate (1M, 50 mL) and aqueous sodium sulphite (1M, 100 ml)
7. washThe organic phase was washed with saturated brine (20 mL)
8. dry with materialdried over sodium sulphate
9. filtrationThe resulting mixture was filtered
10. concentrationthe filtrate concentrated under reduced pressure
11. customto give an orange solid
12. customThe crude solid was purified by chromatography on silica gel (100 g)
13. washeluting with a gradient of ethyl acetate in heptane (10:90 to 50:50)

ORD record

ord-d7ecd29ccd65414da2252afa8fdbe332

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08916593B2