Solketal → 4-(2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-oxo-butyric acid ethyl ester

HRID 1249

Reaktionsgleichung

Reaktionsgleichung von HRID 1249
[H-].[Na+].[CH3:3][C:4]1([CH3:11])[O:8][CH:7]([CH2:9][OH:10])[CH2:6][O:5]1.Cl[CH2:13][C:14](=[O:21])[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17]>O1CCCC1>[CH2:19]([O:18][C:16](=[O:17])[CH2:15][C:14](=[O:21])[CH2:13][O:10][CH2:9][CH:7]1[CH2:6][O:5][C:4]([CH3:11])([CH3:3])[O:8]1)[CH3:20]

Komponenten

5

Edukt 3

HCID 7528SolketalHCID 24758Sodium hydrideHCID 69484Ethyl 4-chloroacetoacetate

Produkt 1

HCID 198712884-(2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-oxo-butyric acid ethyl esterAusbeute 50,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Versuchsvorschrift

To a suspension of sodium hydride (55 g, 60% dispersion in oil) in tetrahydrofuran (1L) under a nitrogen atmosphere was added a solution of 2,2-dimethyl-[1,3]dioxolane-4-methanol (XV, 102.4 g) in tetrahydrofuran (250 mL) over 15 min at room temperature. The resulting mixture was cooled in an ice bath and a solution of ethyl 4-chloroacetoacetate (VIII, 102.9 g) in tetrahydrofuran (250 mL) was added dropwise over a period of 1 h. The reaction mixture was stirred at room temperature for 20 h. The reaction mixture was then quenched with water (100 mL) and tetrahydrofuran was removed under reduced pressure. The aqueous phase was extracted with ethyl acetate (3×250 mL). The combined organic fractions was dried (sodium sulfate), filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (grade 9385, Merck, 230-400 mesh, 60 Å) using a mixture of hexane and ethyl acetate (9:1 and 8:2; 2L each) as eluent, thereby affording the title compound (XVI, 81.6 g). IR (neat, cm-1): 1736. (Alker, D. J. Med. Chem. 1991, 34, 19).

Aufarbeitung

  1. temperatureThe resulting mixture was cooled in an ice bath
  2. customThe reaction mixture was then quenched with water (100 mL) and tetrahydrofuran
  3. customwas removed under reduced pressure
  4. extractionThe aqueous phase was extracted with ethyl acetate (3×250 mL)
  5. dry with materialThe combined organic fractions was dried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography on silica gel (grade 9385, Merck, 230-400 mesh, 60 Å)
  9. additiona mixture of hexane and ethyl acetate (9:1 and 8:2

Quellen und Nachweise

ORD-Eintrag
ord-bcfe7e4ce5914fd798eabd94aed3d84f
Quelldatensatz
uspto-grants-1998_03
Patentnummer
US05723618

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