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

Temperature

-10 °C

To a solution of (pyridin-3-yl)-carbamic acid tert-butyl ester (prepared according to the procedure described in Tetrahedron Lett. 1994, 35, 9003) (2.2 g, 11.3 mmol) in 20 mL of THF at −78° C. is added dropwise t-BuLi (15.4 mL of a 1.7 M solution in pentane, 26 mmol). After 15 minutes, the solution is warmed to −10° C. for 3 hours. The mixture is cooled to −78° C. and a solution of iodine (5.7 g, 22.4 mmol) in 20 mL of THF is added via syringe. The resulting mixture is stirred at −78° C. for 1 hour, then allowed to warm to room temperature and quenched with saturated NH4Cl solution. The aqueous layer is extracted with EtOAc (2×). The combined organic layers are washed with 1 N HCl, water, dilute Na2S2O3, saturated NaHCO3 and saturated NaCl. The organic layer is then dried over MgSO4, filtered and concentrated. The crude product is purified by column chromatography eluting with a gradient of 5% EtOAc/CH2Cl2 to 20% EtOAc/CH2Cl2 to yield the title compound (1.3 g, 4.06 mmol) as a brown solid.

1. temperatureThe mixture is cooled to −78° C.
2. temperatureto warm to room temperature
3. customquenched with saturated NH4Cl solution
4. extractionThe aqueous layer is extracted with EtOAc (2×)
5. washThe combined organic layers are washed with 1 N HCl, water, dilute Na2S2O3, saturated NaHCO3 and saturated NaCl
6. dry with materialThe organic layer is then dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude product is purified by column chromatography
10. washeluting with a gradient of 5% EtOAc/CH2Cl2 to 20% EtOAc/CH2Cl2

ORD record

ord-757ab8d19a374ecfa525a7defb7c502a

Source dataset

uspto-grants-2001_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06281227B1