Potassium Carbonate → HCID 86707728, Verbindung

HRID 1190833Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1190833
[OH:1][C@:2]([CH3:12])([CH2:7][C:8]([O:10]C)=[O:9])[C:3]([O:5]C)=O.ClC(Cl)(Cl)[C:15]([N:17]=C=O)=[O:16].C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[CH3:12][C@:2]1([CH2:7][C:8]([OH:10])=[O:9])[O:1][C:15](=[O:16])[NH:17][C:3]1=[O:5]

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 76400Trichloroacetyl isocyanateHCID 11062924Butanedioic acid, 2-hydroxy-2-methyl-, dimethyl ester, (R)-

Produkt 1

HCID 86707728HCID 86707728, VerbindungAusbeute 25 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of (R)-dimethyl 2-hydroxy-2-methylsuccinate (530 mg, 3.0 mmol) in DCM (10 mL) at 0° C. was added dropwise trichloroacetyl isocyanate (530 mL, 4.5 mmol). The ice bath was removed and the reaction mixture stirred for 2 h then quenched by the addition of MeOH (2 mL) and evaporated under reduced pressure to dryness. To the residue was added 1 M K2CO3 (15 mL, 15 mmol) and the reaction mixture heated at reflux for 0.5 h. The reaction mixture was allowed to cool to rt, extracted with Et2O (2×), then acidified to pH 2 by the addition of 1 N HCl and extracted with EtOAc (3×). The combined extracts were dried (Na2SO4) filtered and concentrated under reduced pressure. The residue was triturated with Et2O, and the triturate evaporated under reduced pressure. The residue was chromatographed by silica gel chromatography eluting with 1 to 10% MeOH/DCM (bromocresol green stain) to give Compound 42a (130 mg, 24% yield) as a clear colorless oil which solidified upon standing. 1H NMR (400 MHz, CDCl3) δ 8.95 (br. s., 1H), 3.14 (d, J=17.3 Hz, 1H), 2.97 (d, J=17.3 Hz, 1H), 1.62 (s, 3H). The structure was confirmed by single crystal X-ray diffraction analysis with material crystallized from Et2O/hexanes.

Aufarbeitung

  1. customThe ice bath was removed
  2. customthen quenched by the addition of MeOH (2 mL)
  3. customevaporated under reduced pressure to dryness
  4. temperaturethe reaction mixture heated
  5. temperatureat reflux for 0.5 h
  6. extractionextracted with Et2O (2×)
  7. additionacidified to pH 2 by the addition of 1 N HCl
  8. extractionextracted with EtOAc (3×)
  9. dry with materialThe combined extracts were dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was triturated with Et2O
  13. customthe triturate evaporated under reduced pressure
  14. customThe residue was chromatographed by silica gel chromatography
  15. washeluting with 1 to 10% MeOH/DCM (bromocresol green stain)

Quellen und Nachweise

ORD-Eintrag
ord-863b7dedd99a421ab5908459c603520a
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08680090B2

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