Chlorosuccinimide → 4,5-Dichloropyridin-2-amine

4-Chloro-2-aminopyridine (Matrix Scientific, cat. #23809; 1.29 g, 0.01 mol) is dissolved by stirring in 500 ml of ethyl acetate. A thermometer is placed in the solution to monitor temperature. N-Chlorosuccinimide (13.3 g, 0.01 mol) is added in several portions to keep the solution at room temperature. The solution becomes dark in color and is stirred at room temperature overnight. The supernatant is decanted from the dark solids that formed and transferred to a separatory funnel. The organic solution is washed with 500 ml saturated aqueous sodium bisulfite and then 500 ml brine. The organic layer is dried with MgSO4 and concentrated on a rotovap. The dark brown crude product is chromatographed on 500 g of flash silica-gel eluting with CH2Cl2. Concentration of the appropriate fractions on a rotovap gives a light tan solid. The solid is dissolved in EtOAc and decolorized with activated carbon. EtoAc is removed using a rotovap and the resulting solid is suspended in ice-cold CH2Cl2 and filtered to give the product as a white solid. (MP 142-143° C.).

1. customat room temperature
2. customThe supernatant is decanted from the dark solids
3. customthat formed
4. customtransferred to a separatory funnel
5. washThe organic solution is washed with 500 ml saturated aqueous sodium bisulfite
6. dry with materialThe organic layer is dried with MgSO4
7. concentrationconcentrated on a rotovap
8. customThe dark brown crude product is chromatographed on 500 g of flash silica-gel
9. washeluting with CH2Cl2
10. customConcentration of the appropriate fractions on a rotovap gives a light tan solid
11. customEtoAc is removed
12. filtrationfiltered

ORD record

ord-40813e47bb624e378918fcbbd4388d7b

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618302B2