Diethyl Malonate → 2-(2-Tert-butoxycarbonylamino-pyridin4-ylmethyl)-malonic acid diethyl ester

HRID 1789796

Reaction equation

HRID 1789796 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]=[C:25]([CH2:27]Br)[CH:24]=[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:25]1[CH:24]=[CH:23][N:22]=[C:21]([NH:20][C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:29])[CH:26]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH3:13]

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 220977361,1-Dimethylethyl N-[4-(bromomethyl)-2-pyridinyl]carbamate

Product 1

HCID 545579702-(2-Tert-butoxycarbonylamino-pyridin4-ylmethyl)-malonic acid diethyl esterYield 62.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of NaH (80%, 0.17 g, 4.00 mmol) in THF (5 mL) at 0° C. under argon was added diethyl malonate (0.64 g, 4.00 mmol). After the mixture was stirred for 15 min the mixture was added to a refluxed mixture of (4-bromomethyl-pyridin-2-yl)-carbamic acid tert-butyl ester (1.00 g, 3.48 mmol) in THF (10 mL), and the mixture was refluxed for 2 h. The mixture was concentrated under reduced pressure and the residue was partitioned between water and chloroform. The organic layer was washed with water and brine and dried. After filtration and evaporation of the solvent, the crude product was purified by flash chromatography (MeOH/CH2Cl2, 1:100) to give 2-(2-tert-butoxycarbonylamino-pyridin4-ylmethyl)-malonic acid diethyl ester (0.80 g, 55%).

Workup

  1. temperaturethe mixture was refluxed for 2 h
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customthe residue was partitioned between water and chloroform
  4. washThe organic layer was washed with water and brine
  5. customdried
  6. filtrationAfter filtration and evaporation of the solvent
  7. customthe crude product was purified by flash chromatography (MeOH/CH2Cl2, 1:100)

Sources & evidence

ORD record
ord-805b1be0b06a48d0ae30146f8f6f791f
Source dataset
uspto-grants-2006_07
Patent number
US07071175B1

Linked notes

Loading…