Nitrogen → 4-(2-Nitrophenyl)pyridine

To a 1 L round-bottomed flask equipped with a reflux condenser was added 2-nitrobenzeneboronic acid (Lancaster) (10 g, 60 mmol), 4-bromopyridine hydrochloride (Fluka) (12 g, 60 mmol), Na2CO3 (25 g, 240 mmol), DME (300 in L) and H2O (100 mL). The mixture was stirred magnetically, degassed in vacuo and purged with N2. The process was repeated five times then tetrakis(triphenylphosphine)-palladium (0) (Strem Chemicals) (3.5 g, 3.0 mmol) was added and the reaction mixture was stirred at reflux under a slight positive pressure of N2 for 15 h. The reaction mixture was concentrated in vacuo and the residue partitioned between EtOAc (100 mL) and satd NaCl (50 mL) diluted with H2O (50 mL). The aqueous phase was further extracted with EtOAc (2×100 mL). The combined organic fractions were extracted with 1 N HCl (3×100 mL). The combined acidic extract was washed with EtOAc (100 mL), cooled in an ice bath and adjusted to pH 10 with 5 N NaOH. The aqueous solution was saturated with NaCl and extracted with EtOAc (3×100 mL). The combined EtOAc extracts were washed with satd NaCl (100 mL), dried over Na2SO4, filtered and concentrated to afford a brown oil. Purification by silica gel chromatography (5:30-65, 1 M NH3/MeOH-EtOAc-hexane) provided the title compound as a viscous, dark orange oil (6.0 g). MS (ESI, pos. ion) m/z: 201 (M+1). Calc'd for C11H8N2O2: 200.19.

1. customTo a 1 L round-bottomed flask equipped with a reflux condenser
2. customdegassed in vacuo
3. custompurged with N2
4. stirringthe reaction mixture was stirred
5. concentrationThe reaction mixture was concentrated in vacuo
6. customthe residue partitioned between EtOAc (100 mL) and satd NaCl (50 mL)
7. additiondiluted with H2O (50 mL)
8. extractionThe aqueous phase was further extracted with EtOAc (2×100 mL)
9. extractionThe combined organic fractions were extracted with 1 N HCl (3×100 mL)
10. extractionThe combined acidic extract
11. washwas washed with EtOAc (100 mL)
12. temperaturecooled in an ice bath
13. extractionextracted with EtOAc (3×100 mL)
14. washThe combined EtOAc extracts were washed with satd NaCl (100 mL)
15. dry with materialdried over Na2SO4
16. filtrationfiltered
17. concentrationconcentrated
18. customto afford a brown oil
19. customPurification by silica gel chromatography (5:30-65, 1 M NH3/MeOH-EtOAc-hexane)

ORD record

ord-b6c877f8fc9e438ea05238085bb08efc

Source dataset

uspto-grants-2005_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06977264B2