Diethyl Malonate → 2-(6-[N,N-bis(tert-butoxycarbonyl)amino]-4-methyl-pyridin-3-ylmethyl)-malonic acid diethyl ester

HRID 1789837Notes

Reaction equation

HRID 1789837 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]([N:21]([C:29]1[CH:34]=[C:33]([CH3:35])[C:32]([CH2:36]Br)=[CH:31][N:30]=1)[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[O:20])([CH3:17])([CH3:16])[CH3:15].C(OCC)(=O)C>CN(C=O)C>[CH2:12]([O:11][C:3](=[O:10])[CH:4]([CH2:36][C:32]1[CH:31]=[N:30][C:29]([N:21]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:20])=[CH:34][C:33]=1[CH3:35])[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH3:13]

Participants

6

Reactant 4

HCID 7761Diethyl MalonateHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 220360082-[N,N-bis(tert-butoxycarbonyl)amino]-5-bromomethyl-4-methyl-pyridin

Product 1

HCID 544595782-(6-[N,N-bis(tert-butoxycarbonyl)amino]-4-methyl-pyridin-3-ylmethyl)-malonic acid diethyl esterYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of NaH (0.24 g, 6.0 mmol, 60%) in DMF (5 mL) was added diethyl malonate (0.91 mL, 6.0 mmol) and the mixture was stirred for 15 min. A solution 2-[N,N-bis(tert-butoxycarbonyl)amino]-5-bromomethyl-4-methyl-pyridin (2.0 g, 5.0 mmol) in DMF (5 mL) was added and the resulting solution stirred for 120 min at 60 ° C. Ethyl acetate was added and the mixture was washed with water and brine and dried. After evaporation of the solvent, the crude product was purified by flash chromatography (CH3OH/CH2Cl2, 1:100→1:20) to give a pure fraction 2-(6-[N,N-bis(tert-butoxycarbonyl)amino]-4-methyl-pyridin-3-ylmethyl)-malonic acid diethyl ester (1.15 g, 48%) and an impure fraction 2-(6-[N,N-bis(tert-butoxycarbonyl)amino]4-methyl-pyridin-3-ylmethyl)-malonic acid diethyl ester (1.1 g).

Workup

  1. stirringthe resulting solution stirred for 120 min at 60 ° C
  2. washthe mixture was washed with water and brine
  3. customdried
  4. customAfter evaporation of the solvent
  5. customthe crude product was purified by flash chromatography (CH3OH/CH2Cl2, 1:100→1:20)

Sources & evidence

ORD record
ord-67ff9859d3e345c2ae19712d6f3b494f
Source dataset
uspto-grants-2006_07
Patent number
US07071175B1

Reaction notes

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