Diethyl Malonate → 2-(2-[N,N-bis(tert-butoxycarbonyl)amino]-pyrimidin-5-ylmethyl)-malonic acid diethyl ester

HRID 1789868Notes

Reaction equation

HRID 1789868 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+].Br[CH2:15][C:16]1[CH:17]=[N:18][C:19]([N:22]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[N:20][CH:21]=1.CCOC(C)=O>CN(C=O)C>[CH2:10]([O:9][C:1](=[O:8])[CH:2]([CH2:15][C:16]1[CH:17]=[N:18][C:19]([N:22]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:23]([O:25][C:26]([CH3:29])([CH3:27])[CH3:28])=[O:24])=[N:20][CH:21]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH3:11]

Participants

6

Reactant 4

HCID 7761Diethyl MalonateHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 22036062N,N-Di-Boc-5-(bromomethyl)pyrimidin-2-amine

Product 1

HCID 544517182-(2-[N,N-bis(tert-butoxycarbonyl)amino]-pyrimidin-5-ylmethyl)-malonic acid diethyl esterYield 48.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A solution of diethyl malonate (0.704 mL, 4.64 mmol) in DMF (2 mL) was added dropwise to a suspention of NaH (200 mg, 4.64 mmol, 55% in mineral oil) in DMF (4 mL) at 0° C. under argon. The reaction mixture was stirred for 30 min and a solution of 5-bromomethyl-2-[N,N-bis(tert-butoxycarbonyl)amino]-pyrimidin (1.5 g, 3.86 mmol) in DMF (4 mL) was added dropwise. The mixture was stirred at room temperature for 3 h. EtOAc was added and the solution was washed with water and brine, dried and concentrated under reduced pressure. Flash chromatography (heptane/EtOAc, 3:2) gave 2-(2-[N,N-bis(tert-butoxycarbonyl)amino]-pyrimidin-5-ylmethyl)-malonic acid diethyl ester (0.87 g, 40%).

Workup

  1. stirringThe mixture was stirred at room temperature for 3 h
  2. washthe solution was washed with water and brine
  3. customdried
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-dd952a3f8bce4f40af135ac1dd2040e3
Source dataset
uspto-grants-2006_07
Patent number
US07071175B1

Reaction notes

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