Diethyl Malonate → 3-Bromo-2-methyl-5-nitropyridine

To a cold solution of diethyl malonate (2.2 mL, 14.5 mmol) in THF (30 mL) was added NaH (0.58 g, 60% in mineral oil) over 5 minutes. 3-Bromo-2-chloro-5-nitropyridine (3.13 g, 13.15 mmol) was added in 4 portions over 15 minutes. The reaction mixture was warmed to room temperature and THF was removed under reduced pressure. The mixture was heated at 115° C. for 75 minutes. After the reaction mixture was cooled to room temperature, H2SO4 (6.0 M, 17 mL) was added and the mixture was heated at 110° C. overnight. It was cooled to 0° C. and a KOH solution (25%) in water was added until pH=7.0. The reaction mixture was kept at 0° C. for 30 min. The crude product was collected by filtration and washed with cold water. dichloromethane (100 mL) was added to the solids and stirred at r.t. for 30 min. The solid was filtered off and the filtrate was concentrated to 30 mL. Petroleum ether (60 mL) was added and the solid was filtered off and the filtrate was concentrated to give the product as a red solid (2.3 g, 73%).

1. customTHF was removed under reduced pressure
2. temperatureThe mixture was heated at 115° C. for 75 minutes
3. temperatureAfter the reaction mixture was cooled to room temperature
4. additionH2SO4 (6.0 M, 17 mL) was added
5. temperaturethe mixture was heated at 110° C. overnight
6. temperatureIt was cooled to 0° C.
7. additiona KOH solution (25%) in water was added until pH=7.0
8. filtrationThe crude product was collected by filtration
9. washwashed with cold water
10. additiondichloromethane (100 mL) was added to the solids
11. filtrationThe solid was filtered off
12. concentrationthe filtrate was concentrated to 30 mL
13. additionPetroleum ether (60 mL) was added
14. filtrationthe solid was filtered off
15. concentrationthe filtrate was concentrated

ORD record

ord-a6da776c53d44a51933e344ba3499d26

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08623889B2