Diethyl Malonate → 2-(6-Tert-butoxycarbonylamino-pyridin-3-ylmethyl)-malonic acid diethyl ester

HRID 1789805Notes

Reaction equation

HRID 1789805 reaction equation
[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[C:14]([O:18][C:19](=[O:29])[NH:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27]Br)=[CH:23][N:22]=1)([CH3:17])([CH3:16])[CH3:15]>C1COCC1>[CH2:12]([O:11][C:3](=[O:10])[CH:4]([CH2:27][C:24]1[CH:23]=[N:22][C:21]([NH:20][C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:29])=[CH:26][CH:25]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH3:13]

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 23030321tert-Butyl (5-(bromomethyl)pyridin-2-yl)carbamate

Product 1

HCID 544806432-(6-Tert-butoxycarbonylamino-pyridin-3-ylmethyl)-malonic acid diethyl esterYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of NaH (0.49 g, 16.3 mmol, 80%) in THF (15 mL) at 0° C. was added diethyl malonate (2.61 g, 16.3 mmol). The mixture was stirred for 15 min and was then added dropwise to a refluxed mixture of (5-bromomethyl-pyridin-2-yl)-carbamic acid tert-butyl ester (3.90 g, 13.6 mmol) in THF (25 mL), and the resulting solution was refluxed for 15 min. After evaporation of the solvent, the crude product was purified by flash chromatography (methanol/CH2Cl2, 1:100→2.5:100) to give 2-(6-tert-butoxycarbonylamino-pyridin-3-ylmethyl)-malonic acid diethyl ester (2.18 g, 44%).

Workup

  1. temperaturethe resulting solution was refluxed for 15 min
  2. customAfter evaporation of the solvent
  3. customthe crude product was purified by flash chromatography (methanol/CH2Cl2, 1:100→2.5:100)

Sources & evidence

ORD record
ord-fdd178d6b86e4eb282f637ab9c2a16a5
Source dataset
uspto-grants-2006_07
Patent number
US07071175B1

Reaction notes

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