反应详情

温度

0 °C

(3-tert-Butoxycarbonylamino-pyridin-4-yl)-oxo-acetic acid ethyl ester was prepared according to a procedure described by Estel, etc (J. Heterocycl. Chem., 1989, 26, 105-): To a solution of pyridin-3-yl-carbamic acid tert-butyl ester (8.50 g, 43.8 mmol) and TMEDA (16.5 mL, 109 mmol) in THF (200 mL) at −78° C. was cannulated tert.-BuLi (64.1 mL, 1.7 M in pentane) over 30 min under nitrogen. The mixture was then stirred for 2 hours between −10° C. and −20° C. After cooling to −60° C. diethyl oxalate (17.8 mL, 131 mmol) was added and the mixture allowed to warm to 0° C. After 3 hours the mixture was poured onto ice/1M HCl (120 mL) and extracted with ethyl acetate (3×150 mL). The combined organic extracts were washed with water (100 mL), brine (75 mL), dried over MgSO4 and concentrated. The residue was purified by flash column chromatography (gradient, hexane/ethyl acetate 5:2, 2:1), to give 3.04 g (24% yield) of compound 146 as a yellow oil.

1. customat −78° C.
2. additionwas added
3. additionAfter 3 hours the mixture was poured onto ice/1M HCl (120 mL)
4. extractionextracted with ethyl acetate (3×150 mL)
5. washThe combined organic extracts were washed with water (100 mL), brine (75 mL)
6. dry with materialdried over MgSO4
7. concentrationconcentrated
8. customThe residue was purified by flash column chromatography (gradient, hexane/ethyl acetate 5:2, 2:1)