Methoxyacetic Acid → N-((5-bromopyridin-2-yl)methyl)-2-methoxyacetamide

A mixture of (5-bromopyridin-2-yl)methanamine (358 mg, 1.914 mmol), 2-methoxyacetic acid (0.191 mL, 2.488 mmol), BOP-reagent (1101 mg, 2.488 mmol) and diisopropylethylamine (1.003 mL, 5.74 mmol) in DMF (8 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)-2-methoxyacetamide (337 mg, 1.301 mmol, 68.0% yield) as an orange oil. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.62 (d, J=2.2 Hz, 1H), 7.79 (dd, J=8.4, 2.4 Hz, 1H), 7.44 (d, J=4.8 Hz, 1H), 7.20 (d, J=8.4 Hz, 1H), 4.56 (d, J=5.5 Hz, 2H), 3.97 (s, 2H), 3.45 (s, 3H). MS (ES+) m/z: 259.0, 261.0 (M+H); LC retention time: 0.907 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-51af902d2774467389b17e504b04485c

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987268B2