Water → 2-[1-(6-tert-Butoxycarbonylamino-pyridin-3-yl)-2-methyl-propyl]-malonic acid monoethyl ester

HRID 1789910Notes

Reaction equation

HRID 1789910 reaction equation
[CH2:1]([O:3][C:4](=[O:29])[CH:5]([CH:11]([C:15]1[CH:16]=[N:17][C:18]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:19][CH:20]=1)[CH:12]([CH3:14])[CH3:13])[C:6]([O:8]CC)=[O:7])[CH3:2].[OH-].[K+].O>ClCCl.C(O)C>[CH2:1]([O:3][C:4](=[O:29])[CH:5]([CH:11]([C:15]1[CH:16]=[N:17][C:18]([NH:21][C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])=[CH:19][CH:20]=1)[CH:12]([CH3:13])[CH3:14])[C:6]([OH:8])=[O:7])[CH3:2]

Participants

6

Reactant 3

HCID 962WaterHCID 14797Potassium HydroxideHCID 543263812-[1-(6-Tert-butoxycarbonylamino-pyridin-3-yl)-2-methyl-propyl]-malonic acid diethyl ester

Product 1

HCID 543314462-[1-(6-tert-Butoxycarbonylamino-pyridin-3-yl)-2-methyl-propyl]-malonic acid monoethyl ester

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-[1-(6-tert-butoxycarbonylamino-pyridin-3-yl)-2-methyl-propyl]-malonic acid diethyl ester (1.569 g, 3.84 mmol) in a mixture of dichloromethane (6 mL) and ethanol (12 mL, 95%) at 0° C. a solution of potassium hydroxide (0.272 g, 85%, 4.2 mmol) in ethanol (6 mL, 95%) was added dropwise over 40 min. After additional 1 h stirring the mixture was allowed to warm up to room temperature and stirring was continued for 18 h. Then water (30 mL) and dichloromethane (30 mL) were added, and after 3 min stirring the layers were separated. The organic was extracted once with water and the combined aqueous were washed once with ether. Then an aqueous solution of citric acid (10%) was added to adjust the pH to 4, and the solution was extracted three times with ethyl acetate. The combined organic layers were washed with brine and dried over magnesium sulphate. After evaporation of the solvent crude 2-[1-(6-tert-butoxycarbonylamino-pyridin-3-yl)-2-methyl-propyl]-malonic acid monoethyl ester (0.94 g, 64%) was obtained.

Workup

  1. additionwas added dropwise over 40 min
  2. stirringstirring
  3. waitwas continued for 18 h
  4. stirringafter 3 min stirring the layers
  5. customwere separated
  6. extractionThe organic was extracted once with water
  7. washthe combined aqueous were washed once with ether
  8. additionThen an aqueous solution of citric acid (10%) was added
  9. extractionthe solution was extracted three times with ethyl acetate
  10. washThe combined organic layers were washed with brine
  11. dry with materialdried over magnesium sulphate
  12. customAfter evaporation of the solvent crude 2-[1-(6-tert-butoxycarbonylamino-pyridin-3-yl)-2-methyl-propyl]-malonic acid monoethyl ester (0.94 g, 64%)
  13. customwas obtained

Sources & evidence

ORD record
ord-531d900b1a5549609a8857c78e89db2d
Source dataset
uspto-grants-2006_07
Patent number
US07071175B1

Reaction notes

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