p-Toluenesulfonic acid monohydrate → HCID 54311538, compound

HRID 376145Notes

Reaction equation

HRID 376145 reaction equation
C(O[CH:4]([O:16]CC)[C:5](=[CH2:15])[CH2:6][O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)C.O.C1(C)C=CC(S(O)(=O)=[O:27])=CC=1.[CH2:31]([O:33][C:34](=[O:38])[CH2:35][N+:36]#[C-:37])[CH3:32]>CC(C)=O.C(Cl)Cl.C1(C)C=CC=CC=1.[Cu-]=O>[CH2:31]([O:33][C:34](=[O:38])[CH:35]([NH:36][CH:37]=[O:27])[CH:4]([OH:16])[C:5](=[CH2:15])[CH2:6][O:7][CH2:8][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[CH3:32]

Participants

8

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 533707Ethyl isocyanoacetateHCID 16093516HCID 16093516, compound

Product 1

HCID 54311538HCID 54311538, compound

Reagents, catalysts & solvents 4

HCID 178419072HCID 178419072, compoundCatalystHCID 180AcetoneSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

4.8 g (19.1 mmol) of 3-benzyloxy-2-methylenepropionaldehyde-diethylacetal and 0.36 g (1.9 mmol) of p-toluenesulfonic acid monohydrate are stirred for 3 hours in 60 ml of acetone. The mixture is diluted with 400 ml of methylene chloride, extracted with N-KHCO3 solution and saturated sodium chloride solution, dried over Na2SO4, filtered and concentrated by evaporation. The 3-benzyloxy-2-methylenepropanol that remains (yellow liquid) is placed at room temperature, without further purification, together with 2.1 ml (19 mmol) of isocyanoacetic acid ethyl ester, in 25 ml of toluene, and 50 mg of copper(I) oxide are added. When the exothermic reaction has subsided, the mixture is stirred for a further one hour at room temperature, filtered over Hyflo® and concentrated by evaporation. The residue is taken up in 25 ml of tetrahydrofuran, 5 ml of water are added, and the mixture is refluxed for 4 hours. The mixture is concentrated by evaporation, toluene is added, and the mixture is again concentrated by evaporation. Chromatography on silica gel with toluene/ethyl acetate (1:1) and subsequent crystallisation from diethyl ether yield 5-benzyloxy-2-formylamino-3-hydroxy-4-methylenepentanoic acid ethyl ester having a melting point of 112°-114° C.

Workup

  1. extractionextracted with N-KHCO3 solution and saturated sodium chloride solution
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated by evaporation
  5. customWhen the exothermic reaction
  6. filtrationfiltered over Hyflo®
  7. concentrationconcentrated by evaporation
  8. addition5 ml of water are added
  9. temperaturethe mixture is refluxed for 4 hours
  10. concentrationThe mixture is concentrated by evaporation, toluene
  11. additionis added
  12. concentrationthe mixture is again concentrated by evaporation
  13. customChromatography on silica gel with toluene/ethyl acetate (1:1) and subsequent crystallisation from diethyl ether

Sources & evidence

ORD record
ord-c6432009b3a34c5c95fc0fb7d4f5f57b
Source dataset
uspto-grants-1996_01
Patent number
US05488140

Reaction notes

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