Potassium Hydroxide → 2-(6-Tert-butoxycarbonylamino-pyridin-3-ylmethyl)-malonic acid monoethyl ester

HRID 1789806Notes

Reaction equation

HRID 1789806 reaction equation
[OH-].[K+].[CH2:3]([O:5][C:6](=[O:28])[CH:7]([CH2:13][C:14]1[CH:15]=[N:16][C:17]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[CH:18][CH:19]=1)[C:8]([O:10]CC)=[O:9])[CH3:4]>C(O)C.C(Cl)Cl>[CH2:3]([O:5][C:6](=[O:28])[CH:7]([CH2:13][C:14]1[CH:15]=[N:16][C:17]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[CH:18][CH:19]=1)[C:8]([OH:10])=[O:9])[CH3:4]

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 544806432-(6-Tert-butoxycarbonylamino-pyridin-3-ylmethyl)-malonic acid diethyl ester

Product 1

HCID 537177962-(6-Tert-butoxycarbonylamino-pyridin-3-ylmethyl)-malonic acid monoethyl esterYield 50%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A solution of KOH (0.37 g, 6.54 mmol) in ethanol (5 mL) was added to a solution of 2-(6-tert-butoxycarbonylamino-pyridin-3-ylmethyl)-malonic acid diethyl ester (2.18 g, 5.95 mmol) in ethanol (25 mL) and methylene chloride (10 mL) at 0° C. The mixture was stirred for 18 h at room temperature. The mixture was concentrated under reduced pressure and the residue dissolved in water. The aqueous layer was washed with ether, acidified to pH 4 by 1M HCl and extracted with methylene chloride. The organic layer was washed with water, brine and dried. After filtration and concentration under reduced pressure, the crude product was purified by flash chromatography (methanol/CH2Cl2, 1:20) to yield 2-(6-tert-butoxycarbonylamino-pyridin-3-ylmethyl)-malonic acid monoethyl ester (1.00 g, 50%).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. dissolutionthe residue dissolved in water
  3. washThe aqueous layer was washed with ether
  4. extractionextracted with methylene chloride
  5. washThe organic layer was washed with water, brine
  6. customdried
  7. filtrationAfter filtration and concentration under reduced pressure
  8. customthe crude product was purified by flash chromatography (methanol/CH2Cl2, 1:20)

Sources & evidence

ORD record
ord-dcc7ced14d924601a79f1709878a8ac1
Source dataset
uspto-grants-2006_07
Patent number
US07071175B1

Reaction notes

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