Ethyl chloroacetate → Ethyl 3-(3-Pyridyl)propanoate

Temperature

0 °C

According to the procedure of B. A. Lefker, W. A. Hada, P. J. McGarry Tetrahedron Lett. 1994, 35, 5205-5208, a solution of sodium bis(trimethylsilyl)amide (1.0 N in THF, 44.3 mL, 44.3 mmol) was added dropwise at a rate to keep the temperature below -50° C. to a stirred solution of 3-pyridine carboxaldehyde (4.41 mL, 46.7 mmol), ethyl chloroacetate (4.93 mL, 46.7 mmol) and THF (34 mL) under a dry nitrogen atmosphere. After 45 min at -78° C., the reaction mixture was warmed to 0° C. and then quenched with water and concentrated. The residue was partitioned between ether and water. The ether phase was dried with brine and concentrated. The residue was dissolved in erthyl acetate and palladium hydroxide on carbon (wet, Degussa type, 20% Pd content, 1 g) was added. The mixture was hydrogenated at 45 psi hydrogen pressure for 2 h. The reaction mixture was filtered thru sulka floc and the solvent was removed. The residue was flash chromatographed (2:3 petroleum ether:ethyl acetate, eluent) to provide the title compound as an oil (3.83 g, 42%): NMR (CDCl3); 8.24 (m, 2 H), 7.60 (d, 1 H), 7.22 (dd, 1 H), 4.45 (t, 1 H), 4.22 (q, 2 H), 3.15 (dd, 1 H), 2.95 (dd, 1 H), 1.27 (t, 3 H).

1. customthe temperature below -50° C.
2. customquenched with water
3. concentrationconcentrated
4. customThe residue was partitioned between ether and water
5. dry with materialThe ether phase was dried with brine
6. concentrationconcentrated
7. dissolutionThe residue was dissolved in erthyl acetate
8. additionpalladium hydroxide on carbon (wet, Degussa type, 20% Pd content, 1 g) was added
9. waitThe mixture was hydrogenated at 45 psi hydrogen pressure for 2 h
10. filtrationThe reaction mixture was filtered thru sulka floc
11. customthe solvent was removed
12. customchromatographed (2:3 petroleum ether:ethyl acetate, eluent)

ORD record

ord-5e506b2d8d5948b0aca99e4b308bdc8f

Source dataset

uspto-grants-2000_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06110962