Reaktion #88027

ord-a4e95bd6a3984fc58b661a90852fe3e1

Lösungsmittel

Reaktionsbedingungen

Temperatur
80°CELSIUS
Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    Temperaturwas heated to 80° C. for 4 hours
  2. 2
    Temperaturheated to 80° C. for additional 2 hours
  3. 3
    SonstigeThe two reaction mixtures
  4. 4
    Sonstigepartitioned between EtOAc and water
  5. 5
    ExtraktionThe aqueous phase was extracted with EtOAc
  6. 6
    Waschenthe combined organic layers were washed several times with brine
  7. 7
    Trocknendried over sodium sulfate
  8. 8
    Filtrationfiltered
  9. 9
    Einengenconcentrated to dryness
  10. 10
    SonstigeThe residue was purified by flash chromatography on silica gel (petroleum ether/EtOAc=6/4 to EtOAc 100%)

Vorschrift

A mixture of tert-butyl 5-(methylsulfonamido)thiophene-2-carboxylate (int. 56) (773 mg, 2.79 mmol), 4-(2-chloroethyl)morpholine hydrochloride (778 mg, 4.18 mmol) and K2CO3 (963 mg, 6.97 mmol) in DMF (30 ml) was heated to 80° C. for 6 hours. In parallel a mixture of tert-butyl 5-(N-(methylsulfonyl)methylsulfonamido)thiophene-2-carboxylate (Int. 57) (420 mg, 1.182 mmol), 4-(2-chloroethyl)morpholine hydrochloride (330 mg, 1.772 mmol) and K2CO3 (408 mg, 2.95 mmol) in DMF (15 ml) was heated to 80° C. for 4 hours, stirred at RT overnight and heated to 80° C. for additional 2 hours. The two reaction mixtures were combined and partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc and the combined organic layers were washed several times with brine, dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by flash chromatography on silica gel (petroleum ether/EtOAc=6/4 to EtOAc 100%) to afford tert-butyl 5-(N-(2-morpholinoethyl)methylsulfonamido)-thiophene-2-carboxylate (Int. 58) (1.3 g, 3.33 mmol, MS/ESI+391.0 [MH]+).

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US09440954B2uspto-grants-2016_09