Diethyl Oxalate → (3-tert-Butoxycarbonylamino-pyridin-4-yl)-oxo-acetic acid ethyl ester
Reaction equation
[C:1]([O:5][C:6](=[O:14])[NH:7][C:8]1[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].CN(CCN(C)C)C.[Li]CCCC.[C:28](OCC)(=[O:34])[C:29]([O:31][CH2:32][CH3:33])=[O:30]>C1COCC1>[CH2:32]([O:31][C:29](=[O:30])[C:28]([C:13]1[CH:12]=[CH:11][N:10]=[CH:9][C:8]=1[NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:14])=[O:34])[CH3:33]Participants
Conditions
- Temperature
- 0 °C
Procedure
(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.
Workup
- customat −78° C.
- additionwas added
- additionAfter 3 hours the mixture was poured onto ice/1M HCl (120 mL)
- extractionextracted with ethyl acetate (3×150 mL)
- washThe combined organic extracts were washed with water (100 mL), brine (75 mL)
- dry with materialdried over MgSO4
- concentrationconcentrated
- customThe residue was purified by flash column chromatography (gradient, hexane/ethyl acetate 5:2, 2:1)
Sources & evidence
- ORD record
- ord-3f317b1bb2ba4f84a3f4b4a43cb7f1ef
- Source dataset
- uspto-grants-2004_08
- Patent number
- US06774134B2
Reaction notes
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