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

Temperature

-75 °C

In heat-dried argon purged 4-neck flask was placed a solution of pyridin-3-yl-carbamic acid tert-butyl ester (10 g, 51.5 mmol, CAS RN 56700-70-0) in THF (100 mL). After cooling down to −75° C., tert-butyllithium (1.7M solution in n-pentane, 66.6 mL, 113 mmol) was added dropwise over 15 min keeping the temperature below −60° C. The resulting light brown suspension was stirred at −75° C. for 3.75 h. A solution of iodine (28.7 g, 113 mmol) in THF (50 mL) was added dropwise over 20 min. below −63° C. The reaction mixture was stirred at −75° C. for 1.5 h and then poured on saturated aqueous NH4Cl solution (1000 mL) and EtOAc (500 mL). The layers were separated. The organic layer was washed once with 10% aqueous Na2S2O3 solution (300 mL) and once with brine (250 mL), dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 120 g column using a MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). Yellow solid (11.7 g; 71%). MS (ESI): m/z=321.1 [M+H]+.

1. customIn heat-dried argon purged 4-neck flask was placed
2. customthe temperature below −60° C
3. stirringThe reaction mixture was stirred at −75° C. for 1.5 h
4. customThe layers were separated
5. washThe organic layer was washed once with 10% aqueous Na2S2O3 solution (300 mL) and once with brine (250 mL)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. additiontreated with silica gel
9. customevaporated
10. customThe compound was purified by silica gel chromatography on a 120 g column
11. washeluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)

ORD record

ord-d986a837971249c59a9fde24d31c9d88

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987307B2