Dimethyl Carbonate → Methyl (2-chloropyridin-4-yl)acetate

Participants

Reaction Conditions

Reaction Steps

A solution of LDA (1.8M in THF/heptane/ethyl benzene, 223 ml, 401 mmol) was added slowly to a stirred solution of 2-chloro-4-methylpyridine (17.5 ml, 200 mmol) in dry THF (1 L) under N2, such that the internal temperature <−70° C. After 1 hour at this temperature, dimethyl carbonate (40 ml, 475 mmol) was added. After 30 minutes the reaction was transferred to a cold bath at −40° C., and then allowed to warm slowly to 0° C. After 1 hour at 0° C. the reaction was quenched with saturated aqueous NH4Cl (250 ml). The mixture was partitioned between EtOAc/H2O. The aqueous layer was extracted with EtOAc (×2). The combined extracts were washed with brine (×1), then dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography on silica, eluting with 10-25% EtOAc/isohexane to give the ester (27.8 g, 75%) as a pale yellow liquid. 1H NMR (400 MHz, CDCl3) δ: 3.63 (2H, s), 3.73 (3H, s), 7.17 (1H, dd, J 5.1, 1.4), 7.28 (1H, s), 8.34 (1H, d, J 5.1).

Provenance & Evidence