반응 #88027

ord-a4e95bd6a3984fc58b661a90852fe3e1

용매

반응 조건

온도
80°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도was heated to 80° C. for 4 hours
  2. 2
    온도heated to 80° C. for additional 2 hours
  3. 3
    기타The two reaction mixtures
  4. 4
    기타partitioned between EtOAc and water
  5. 5
    추출The aqueous phase was extracted with EtOAc
  6. 6
    세척the combined organic layers were washed several times with brine
  7. 7
    건조dried over sodium sulfate
  8. 8
    여과filtered
  9. 9
    농축concentrated to dryness
  10. 10
    기타The residue was purified by flash chromatography on silica gel (petroleum ether/EtOAc=6/4 to EtOAc 100%)

실험 절차

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]+).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US09440954B2uspto-grants-2016_09