Isobutyric Acid → N-((5-bromopyridin-2-yl)methyl)isobutyramide

A mixture of (5-bromopyridin-2-yl)methanamine (200 mg, 1.069 mmol), isobutyric acid (0.159 mL, 1.711 mmol), BOP-reagent (757 mg, 1.711 mmol) and diisopropylethylamine (0.747 mL, 4.28 mmol) in DMF (6 mL) was stirred at rt for 2 hr. The reaction mixture was partitioned between EtOAc (60 ml) and saturated NaHCO3 solution (60 ml). The organic layer was washed with 10% LiCl solution (2×50 ml) and brine (50 ml). After drying (MgSO4) and filtration, the organic layer was concentrated to afford an orange oil that was chromatographed on a 24 gm ISCO silica gel cartridge, eluting with a 0-100% EtOAc/Hex gradient. The pure fractions were concentrated to afford N-((5-bromopyridin-2-yl)methyl)isobutyramide (230 mg, 0.894 mmol, 84% yield) as an orange oil. 1H NMR (400 MHz, METHANOL-d4) δ 8.57 (d, J=2.2 Hz, 1H), 7.95 (dd, J=8.4, 2.4 Hz, 1H), 7.26 (d, J=8.4 Hz, 1H), 4.42 (s, 2H), 2.53 (dt, J=13.8, 6.8 Hz, 1H), 1.15 (d, J=6.8 Hz, 6H). MS (ES+) m/z: 257.0, 259.0 (M+H); LC retention time: 1.200 min (analytical HPLC Method O).

1. customThe reaction mixture was partitioned between EtOAc (60 ml) and saturated NaHCO3 solution (60 ml)
2. washThe organic layer was washed with 10% LiCl solution (2×50 ml) and brine (50 ml)
3. customAfter drying
4. filtration(MgSO4) and filtration
5. concentrationthe organic layer was concentrated
6. customto afford an orange oil that
7. customwas chromatographed on a 24 gm ISCO silica gel cartridge
8. washeluting with a 0-100% EtOAc/Hex gradient
9. concentrationThe pure fractions were concentrated

ORD record

ord-bc156e0caaef43eab6711baed5b85793

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987268B2