Ethyl 2-pyridineglyoxylate → Ethyl 2-hydroxy-2-(2-pyridyl)acetate

A stirred solution of ethyl 2-oxo-(pyridin-2-yl)acetate (1.0 g, 5.6 mmol) in THF (15 mL) was cooled to −78° C. under an atmosphere of nitrogen. To this solution was added methyl magnesium bromide in THF (6.2 mL of a 1.0 M solution, 6.2 mmol) dropwise over 5 min. The cooling bath was removed and the stirred mixture was allowed to warm to ambient temperature over 2 h. Water (30 mL) was added and the mixture was extracted with EtOAc (50 mL). The organic phase was washed with brine, dried over anhydrous MgSO4, filtered, and the solvent was removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography using 1:2 EtOAc:hexanes as eluant. Product-containing fractions were combined and the solvents were removed under reduced pressure to give ethyl 2-hydroxy-2-(2-pyridyl)acetate as a colorless liquid (0.90 g, 83%; HPLC RT=1.46 min, method A; TLC Rf=0.3 (1:2 EtOAc:hex); LCMS m/z=196; 1H NMR (400 MHz, CDCl3): δ 8.55 (dd, J=0.9, 4.8 Hz, 1H), 7.74 (dt, Jd=1.1 Hz, Jt=8.0 Hz, 1H), 7.57 (d, J=8.0 Hz, 1H), 7.26 (dd, J=4.5, 8.0 Hz, 1H), 5.45 (s, 1H), 4.19 (q, J=7.0 Hz, 2H), 1.82 (s, 3H), 1.23 (t, J=7.0 Hz, 3H)).

1. customThe cooling bath was removed
2. additionWater (30 mL) was added
3. extractionthe mixture was extracted with EtOAc (50 mL)
4. washThe organic phase was washed with brine
5. dry with materialdried over anhydrous MgSO4
6. filtrationfiltered
7. customthe solvent was removed under reduced pressure
8. customThe residue was purified by pressurized silica gel column chromatography
9. customthe solvents were removed under reduced pressure

ORD record

ord-eba0de2bb9ee4c42b30a6ab052e2d8a4

Source dataset

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07144899B2