Nitrogen → Ethyl 3-(5-bromopyridin-2-yl)propanoate

Temperature

90 °C

A solution of Zn metal (18 g, 0.27 mol) in DMF (5 mL) was purged with N2. BrCH2CH2Br (2.0 g, 10 mmol) was added, followed by TMSCl (0.92 g, 8.5 mmol). The resulting mixture was stirred at 90° C. for 30 min, and allowed to cool to rt. A solution of compound 57a (50 g, 0.22 mol) in DMF (150 mL) was added, and the resulting mixture was stirred overnight at rt. Pd(PPh3)2Cl2 (7.4 g, 10 mmol) was added, followed by 2,5-dibromopyridine (50 g, 0.21 mol). The resulting mixture was stirred at 68° C. for 2 h. The reaction was quenched by the addition of saturated NaHCO3 solution (300 mL). The resulting solution was extracted with EtOAc (2×100 mL), and the combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue obtained was purified by flash column chromatography on silica gel (EtOAc/petroleum ether (1:2 v/v)) to obtain compound 57b as a yellow oil. Mass Spectrum (LCMS, ESI pos.): Calcd. for C10H12BrNO2: 258.0 (M+H). Found: 258.2.

1. temperatureto cool to rt
2. stirringthe resulting mixture was stirred overnight at rt
3. stirringThe resulting mixture was stirred at 68° C. for 2 h
4. customThe reaction was quenched by the addition of saturated NaHCO3 solution (300 mL)
5. extractionThe resulting solution was extracted with EtOAc (2×100 mL)
6. dry with materialthe combined organic layers were dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue obtained
10. customwas purified by flash column chromatography on silica gel (EtOAc/petroleum ether (1:2 v/v))

ORD record

ord-f2a3c4df615449af8303039789745376

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09193736B2