Diethyl Malonate → HCID 53978298, compound

HRID 1789881Notes

Reaction equation

HRID 1789881 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[C:26]([Cl:27])=[CH:25][C:24]([CH2:28]Br)=[CH:23][N:22]=1)([CH3:17])([CH3:16])[CH3:15].[NH4+].[Cl-]>CN(C=O)C.O.C(Cl)Cl>[CH2:10]([O:9][C:1](=[O:8])[CH:2]([CH2:28][C:24]1[CH:23]=[N:22][C:21]([NH:20][C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:30])=[C:26]([Cl:27])[CH:25]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH3:11]

Participants

7

Reactant 4

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 53695021HCID 53695021, compound

Product 1

HCID 53978298HCID 53978298, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 21908982Water methylene chlorideSolvent

Procedure

Diethyl malonate (1.87 ml, 12.31 mmol) was added to a suspension of NaH (0.54 g, 12.31 mmol, 55%) in dry DMF (15 ml) at −8° C. This mixture was stirred for 15 min. before it was added dropwise to a solution of (5-bromomethyl-3-chloro-pyridin-2-yl)-carbamic acid tert-butyl ester (3.30 g, 10.26 mmol) in dry DMF (50 ml) at 0° C. The resulting solution was stirred for 40 minutes at 0° C., then NH4Cl (5 ml, sat.) was added carefully. Stirring at room temperature overnight and concentration under reduced pressure gave a residue, which was dissolved in water/CH2Cl2. The aqueous layer was extracted with CH1Cl2 and the combined organic extracts were dried, filtered and concentrated under reduced pressure. Flash chromatography (1% MeOH in CH2Cl2) gave 2-(6-tert-butoxycarbonylamino-5-chloro-pyridin-3-ylmethyl)-malonic acid diethyl ester (2.45, 60%) as a sticky clear oil.

Workup

  1. stirringThe resulting solution was stirred for 40 minutes at 0° C.
  2. stirringStirring at room temperature overnight
  3. concentrationconcentration under reduced pressure
  4. customgave a residue, which
  5. extractionThe aqueous layer was extracted with CH1Cl2
  6. customthe combined organic extracts were dried
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f8bd0dd4478c4b95809d11c933abc152
Source dataset
uspto-grants-2006_07
Patent number
US07071175B1

Reaction notes

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