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

Temperature

-78 °C

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)+.

1. stirringThe red solution was stirred at −78° C. for 15 min
2. customwas quenched with half-saturated NH4Cl (175 mL)
3. temperatureThe mixture was warmed to +5° C.
4. extractionextracted with EtOAc (175 mL)
5. washThe combined organics were washed with brine (100 mL)
6. dry with materialdried (MgSO4)
7. concentrationconcentrated
8. customThe cloudy yellow oil was chromatographed on silica gel (15% EtOAc/hexanes)

ORD record

ord-a33a5c89a5ad4b91a747cafa9b45e413

Source dataset

uspto-grants-2003_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06576643B2