Sodium hydride → 1-Tert-butyl 3-ethyl 2-(6-nitropyridin-3-yl)malonate

HRID 2173310Notes

Reaction equation

[H-].[Na+].[C:3]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].Cl[C:17]1[CH:18]=[CH:19][C:20]([N+:23]([O-:25])=[O:24])=[N:21][CH:22]=1>CN(C=O)C>[N+:23]([C:20]1[N:21]=[CH:22][C:17]([CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]([O:11][C:12]([CH3:14])([CH3:13])[CH3:15])=[O:10])=[CH:18][CH:19]=1)([O-:25])=[O:24]

Participants

Conditions

Temperature: 80 °C

Procedure

To a suspension of NaH (60% in oil, 0.650 g, 16.4 mmol) in DMF (40 mL) was added tert-butyl ethyl propanedioate (2.8 g, 15.1 mmol) at room temperature. The mixture was stirred for 30 min. A solution of 5-chloro-2-nitropyridine (2.00 g, 12.6 mmol) in DMF (10 mL) was added. The mixture was heated to 80° C. and stirred for 4 hours. The solvent was removed under reduce pressure. Water was added and the mixture was extracted with EtOAc. The combined organic layer was washed with brine, dried over anhydrous Na2SO4, concentrated and the residue was purified by column chromatography with silca gel to give tert-butyl ethyl (6-nitropyridin-3-yl)propanedioate. 1H-NMR (400 MHz, CDCl3) δ 8.58 (s, 1H), 8.20˜8.27 (m, 2H), 4.69 (s, 1H), 4.21˜4.26 (m, 2H), 1.45 (s, 9H), 1.28 (t, J=7.2 Hz, 2H).

Workup

stirringstirred for 4 hours
customThe solvent was removed
additionWater was added
extractionthe mixture was extracted with EtOAc
washThe combined organic layer was washed with brine
dry with materialdried over anhydrous Na2SO4
concentrationconcentrated
customthe residue was purified by column chromatography with silca gel

Sources & evidence

ORD record: ord-354fa46cc26f424f9b31323cb457b393
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09056859B2

Reaction notes

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