2,6-Lutidine → t-butyl (RS)-2-chloro-2-((3R,4R)-3-phenylacetamido-4-[(RS)-tetrahydropyran-2-ylcarbonylmethylthio]azetidin-2-on-1-yl]acetate

HRID 376563Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 376563
O[CH:2]([N:10]1[C@H:13]([S:14][CH2:15][C:16]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)=[O:17])[C@H:12]([NH:24][C:25](=[O:33])[CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:11]1=[O:34])[C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].N1C(C)=CC=CC=1C.S(Cl)([Cl:45])=O.C(OCC)(=O)C>C1COCC1>[Cl:45][CH:2]([N:10]1[C@H:13]([S:14][CH2:15][C:16]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)=[O:17])[C@H:12]([NH:24][C:25](=[O:33])[CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:11]1=[O:34])[C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4]

Komponenten

6

Edukt 4

HCID 79372,6-LutidineHCID 8857Ethyl AcetateHCID 24386Thionyl ChlorideHCID 18397160t-Butyl 2-hydroxy-2-[(3R,4R)-3-phenylacetamido-4-[(RS)-tetrahydropyran-2-ylcarbonylmethylthio]azetidin-2-on-1-yl]acetate

Produkt 1

HCID 54090620t-butyl (RS)-2-chloro-2-((3R,4R)-3-phenylacetamido-4-[(RS)-tetrahydropyran-2-ylcarbonylmethylthio]azetidin-2-on-1-yl]acetate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

t-Butyl 2-hydroxy-2-[(3R,4R)-3-phenylacetamido-4-[(RS)-tetrahydropyran-2-ylcarbonylmethylthio]azetidin-2-on-1-yl]acetate (1.9g) in dry THF (10ml) was treated with 2,6-lutidine (0.62g, 0.67ml) followed by thionyl chloride (0.69g, 0.42ml) in THF (5ml) dropwise at <-20° C. under argon. The reaction mixture was allowed to warm slowly to ca 0° C. at which point no starting material was observed by t.l.c. (ethyl acetate). The reaction mixture was filtered and solvent removed in vacuo, the residue dissolved in toluene and evaporated to afford crude t-butyl (RS)-2-chloro-2-((3R,4R)-3-phenylacetamido-4-[(RS)-tetrahydropyran-2-ylcarbonylmethylthio]azetidin-2-on-1-yl]acetate as a brown gum. This was dissolved in dry dioxan (10ml) and treated with tri-n-butylphosphine (1.79g, 2.2ml). The reaction mixture was stirred until loss of starting material was observed by t.l.c. (ethyl acetate) ca 0.5h. After removal of solvent in vacuo the title compound was obtained by flash chromatography (eluting with 50,60,80% ethyl acetate in hexane, ethyl acetate) as a pale brown foam (1.95g, 75%); vmax (CH2Cl2) 3417(w), 1762, 1681, 1625cm-1. [Mass spectrum +ve ion (thioglycerol) MH+ (677)].

Aufarbeitung

  1. temperatureto warm slowly to ca 0° C. at which point no starting material
  2. filtrationThe reaction mixture was filtered
  3. customsolvent removed in vacuo
  4. dissolutionthe residue dissolved in toluene
  5. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-9281b7a331e94a40b644e5d6a55fc508
Quelldatensatz
uspto-grants-2000_02
Patentnummer
US06020329

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