Potassium Hydroxide → 2-[1-(6-Tert-butoxycarbonylamino-pyridin-3-yl)-propyl]-malonic acid monoethyl ester

HRID 1789907Notes

Reaction equation

HRID 1789907 reaction equation
[CH2:1]([O:3][C:4](=[O:28])[CH:5]([CH:11]([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)[CH2:12][CH3:13])[C:6]([O:8]CC)=[O:7])[CH3:2].[OH-].[K+]>ClCCl.C(O)C>[CH2:1]([O:3][C:4](=[O:28])[CH:5]([CH:11]([C:14]1[CH:15]=[N:16][C:17]([NH:20][C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])=[CH:18][CH:19]=1)[CH2:12][CH3:13])[C:6]([OH:8])=[O:7])[CH3:2]

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 544316442-[1-(6-Tert-butoxycarbonylamino-pyridin-3-yl)-propyl]-malonic acid diethyl ester

Product 1

HCID 541756692-[1-(6-Tert-butoxycarbonylamino-pyridin-3-yl)-propyl]-malonic acid monoethyl esterYield 82.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

2-[1-(6-tert-Butoxycarbonylamino-pyridin-3-yl)-propyl]-malonic acid diethyl ester (3.23 g, 8.19 mmol) was dissolved in a mixture of dichloromethane (12 mL) and ethanol (24 mL, 99.5%). To this solution was added dropwise a solution of potassium hydroxide (0.528 g, 87%, 8.20 mmol) in ethanol (16 mL, 99.5%) at 0° C. over 0.5 h. Stirring was continued for 16 h while the mixture was allowed to warn up to room temperature. After concentration under reduced pressure to 5-10 mL, water (50 mL) was added and the resulting emulsion was stirred for 0.5 h, and then filtered. The filtrate was washed twice with a mixture of ethyl acetate and diethyl ether (2:1, vol/vol). The aqueous layer was acidified by addition of a solution of citric acid in water (10%) to reach a pH of 4 to 5, and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulphate, and the solvent was removed under reduced pressure to yield 2-[1-(6-tert-butoxycarbonylamino-pyridin-3-yl)-propyl]-malonic acid monoethyl ester (2.47 g, 82%)

Workup

  1. customto warn up to room temperature
  2. concentrationAfter concentration under reduced pressure to 5-10 mL, water (50 mL)
  3. additionwas added
  4. stirringthe resulting emulsion was stirred for 0.5 h
  5. filtrationfiltered
  6. washThe filtrate was washed twice with a mixture of ethyl acetate and diethyl ether (2:1, vol/vol)
  7. additionThe aqueous layer was acidified by addition of a solution of citric acid in water (10%)
  8. extractionextracted three times with ethyl acetate
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried over magnesium sulphate
  11. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-83f8b8280796475cbefda10db2bad030
Source dataset
uspto-grants-2006_07
Patent number
US07071175B1

Reaction notes

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