Reaktion #48414

ord-c6a1db191d1940439816ea7d8c87c849

Lösungsmittel

Reaktionsbedingungen

Temperatur
-30°CELSIUS
Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    workup.ADDITIONwere added
  2. 2
    SonstigeThe reaction was quenched with water
  3. 3
    Extraktionthe mixture was extracted with ethyl acetate
  4. 4
    WaschenThe organic layer was washed with water (3×), saturated brine
  5. 5
    Trocknendried over magnesium sulfate
  6. 6
    Filtrationfiltered
  7. 7
    Einengenconcentrated
  8. 8
    SonstigePurification by silica gel chromatography (0% ethyl acetate/hexanes→50% ethyl acetate/hexanes)

Vorschrift

Sodium hydride (60% dispersion in mineral oil; 40 mg, 0.600 mmol) was added to a solution of tert-butyl (3R,6S)-6-(2,3-difluorophenyl)-2-oxoazepan-3-ylcarbamate (170 mg, 0.500 mmol) in N,N-dimethylformamide (4 mL) at 0° C. After 5 min the mixture was cooled to −30° C. and 1-iodo-2-(methylthio)ethane [prepared according to known procedures: J. Org. Chem., 1987, 52, 2299-2301 (158 mg, 0.782 mmol)] was added. Additional sodium hydride (33 mg, 0.50 mmol) was added and after 4 h excess sodium hydride (33 mg, 0.50 mmol) and 1-iodo-2-(methylthio)ethane (75.6 mg, 0.374 mmol) were added. After 3 h, the final portions of sodium hydride (33 mg, 0.50 mmol) and 1-iodo-2-(methylthio)ethane (75.6 mg, 0.374 mmol) were added and the mixture stirred at −20° C. overnight. The reaction was quenched with water and the mixture was extracted with ethyl acetate. The organic layer was washed with water (3×), saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (0% ethyl acetate/hexanes→50% ethyl acetate/hexanes) gave the title compound (77 mg). MS 415 (M+1).

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07745427B2uspto-grants-2010_06