N-methyl-2-pyrrolidone → HCID 10466854, compound

Temperature

-78 °C

A solution of BuLi (16.9 mmol) in hexanes (1.6 M, 10.6 ml) was added to a stirred solution of 2,5-dibromopyridine (40 g, 16.9 mmol) in Et2O (300 ml) at −78° C. under N2. The resulting suspension was then stirred at −78° C. for 1 h. N-Methyl pyrrolidinone (1.62 ml, 16.9 mmol) was added and the reaction allowed to warm slowly to room temperature and then stirred at RT for a further 1 h. NH4Cl solution (50 ml) was added and the organics were extracted with Et2O (3×100 ml). The combined organics were washed with brine (50 ml) and then concentrated under reduced pressure. The crude residue was taken up in 1,2-dichloroethane (50 ml), sodium triacetoxyborohydride (3.94 g, 16.9 mmol) was added portionwise and then the reaction mixture was stirred at room temperature overnight. 2 N NaOH solution (50 ml) was added and the organics were extracted with CH2Cl2 (3×100 ml), dried (MgSO4), and concentrated under reduced pressure. The resulting crude residue was purified by column chromatography on silica using 3% MeOH/CH2Cl2 containing 1% NH3 to yield the desired pyridine (480 mg, 10%). m/z (ES+) 241, 243 (1:1, M+H+).

1. temperatureto warm slowly to room temperature
2. stirringstirred at RT for a further 1 h
3. extractionthe organics were extracted with Et2O (3×100 ml)
4. washThe combined organics were washed with brine (50 ml)
5. concentrationconcentrated under reduced pressure
6. stirringthe reaction mixture was stirred at room temperature overnight
7. extractionthe organics were extracted with CH2Cl2 (3×100 ml)
8. dry with materialdried (MgSO4)
9. concentrationconcentrated under reduced pressure
10. customThe resulting crude residue was purified by column chromatography on silica using 3% MeOH/CH2Cl2 containing 1% NH3
11. customto yield the desired pyridine (480 mg, 10%)

ORD record

ord-caf802387a3b4006ac86e0b43e79de03

Source dataset

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06900209B2