Diethyl Carbonate → Ethyl-6-[(tert-butoxycarbonyl)methylamino]-2-pyridylacetate

Participants

Reaction Conditions

Reaction Steps

LDA was prepared at 0° C. under argon from diisopropylamine (19.5 mL, 139.14 mmole) and 2.5 M n-BuLi in hexanes (46.4 mL, 115.95 mmole) in dry THF (350 mL). This solution was cooled to −78° C. and a solution of 2-[(tert-butoxycarbonyl)methylamino]-6-picoline (10.31 g, 46.38 mmole) in dry THF (46 mL) was added dropwise over 10 min. Additional dry THF (2 mL) was used in transfer. The orange solution was stirred at −78° C. for 15 min, then diethyl carbonate (6.2 mL, 51.02 mmole) was added rapidly. The red solution was stirred at −78° C. for 15 min, then was quenched with half-saturated NH4Cl (175 mL). The mixture was warmed to +5° C. and extracted with EtOAc (175 mL) then with CH2Cl2 (2×100 mL). The combined organics were washed with brine (100 mL), dried (MgSO4), and concentrated. The cloudy yellow oil was chromatographed on silica gel (15% EtOAc/hexanes) to afford the title compound (10.72 g, 79%) as a light yellow oil: 1H NMR (250 MHz, CDCl3) δ7.51-7.63 (m, 2 H), 6.91-7.03 (m, 1 H), 4.19 (q, J=7.1 Hz, 2 H), 3.77 (s, 2 H), 3.38 (s, 3 H), 1.27 (t, J=7.1 Hz, 3 H), 1.51 (s, 9 H); MS (ES) m/e 295 (M+H)+.

Provenance & Evidence