Iodine → [1-(6-Chloro-4-iodo-pyridin-3-yl)-ethyl]-carbamic acid tert-butyl ester

Temperature

-78 °C

Dissolve tert-butyl 1-(6-chloropyridin-3-yl)ethylcarbamate (3.77 g, 14.7 mmol) in THF (60 mL). Add tert-butyllithium (1.7 M heptane solution, 25.9 mL, 44.0 mmol) at −78° C. under N2. Stir the reaction solution for 0.5 h at −78° C. Add a solution of iodine (5.59 g, 22.0 mmol) in THF (44 mL) dropwise over 30 min under N2 at −78° C. Stir the resulting solution at −78° C. for 1 h, then from −78° C. to RT for 1 h. Quench the reaction with water. Extract with ethyl acetate. Wash the organic layer with water and saturated aqueous sodium chloride. Dry over MgSO4. After filtration, concentrate and purify the crude by FCC (0.1% to 1% 2 M NH3 methanol solution/CH2Cl2) to afford the title compound (1.34 g, 24%) with 98% HPLC purity. MS (ES) m/z 383 [M+1]+

1. customat −78° C.
2. stirringStir the resulting solution at −78° C. for 1 h
3. waitfrom −78° C. to RT for 1 h
4. customQuench
5. customthe reaction with water
6. extractionExtract with ethyl acetate
7. washWash the organic layer with water and saturated aqueous sodium chloride
8. dry with materialDry over MgSO4
9. filtrationAfter filtration
10. concentrationconcentrate
11. custompurify the crude by FCC (0.1% to 1% 2 M NH3 methanol solution/CH2Cl2)

ORD record

ord-9d381872a5ae4e6e935ab5c84f080274

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08114872B2