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

HRID 1789860Notes

Reaction equation

HRID 1789860 reaction equation
[C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].[C:14]([O:18][C:19](=[O:30])[NH:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27]Br)=[C:23]([CH3:29])[N:22]=1)([CH3:17])([CH3:16])[CH3:15].CCOC(C)=O>CN(C=O)C>[CH2:10]([O:9][C:1](=[O:8])[CH:2]([CH2:27][C:24]1[C:23]([CH3:29])=[N:22][C:21]([NH:20][C:19]([O:18][C:14]([CH3:16])([CH3:15])[CH3:17])=[O:30])=[CH:26][CH:25]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH3:11]

Participants

6

Reactant 4

HCID 7761Diethyl MalonateHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 53794246Tert-butyl (5-(bromomethyl)-6-methylpyridin-2-YL)carbamate

Product 1

HCID 696502982-(6-Tert-butoxycarbonylamino-2-methyl-pyridin-3-ylmethyl)-malonic acid diethyl esterYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A solution of diethyl malonate (1.21 mL, 7.97 mmol) in DMF (2 mL) was added dropwise to a suspention of NaH (348 mg, 7.97 mmol, 55% in mineral oil) in DMF (5 mL) at 0 ° C. under argon. The reaction mixture was stirred for 45 min and a solution of (5-bromomethyl-6-methyl-pyridin-2-yl)-carbamic acid tert-butyl ester (2.0 g, 6.64 mmol) in DMF (5 mL) was added dropwise. The mixture was stirred over night (0° C.→20° C.). EtOAc was added and the solution was washed with water and brine, dried and concentrated under reduced pressure. Flash chromatography (heptane/EtOAc, 4:1) gave 2-(6tert-butoxycarbonylamino-2-methyl-pyridin-3-ylmethyl)-malonic acid diethyl ester (1.87 g, 74%).

Workup

  1. stirringThe mixture was stirred over night (0° C.→20° C.)
  2. washthe solution was washed with water and brine
  3. customdried
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e3f6a6dfc7f54f738769feb1bbdfdd3b
Source dataset
uspto-grants-2006_07
Patent number
US07071175B1

Reaction notes

Loading…