反応 #88027

ord-a4e95bd6a3984fc58b661a90852fe3e1

溶媒

反応条件

温度
80°CELSIUS
詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    温度was heated to 80° C. for 4 hours
  2. 2
    温度heated to 80° C. for additional 2 hours
  3. 3
    その他The two reaction mixtures
  4. 4
    その他partitioned between EtOAc and water
  5. 5
    抽出The aqueous phase was extracted with EtOAc
  6. 6
    洗浄the combined organic layers were washed several times with brine
  7. 7
    乾燥dried over sodium sulfate
  8. 8
    ろ過filtered
  9. 9
    濃縮concentrated to dryness
  10. 10
    その他The residue was purified by flash chromatography on silica gel (petroleum ether/EtOAc=6/4 to EtOAc 100%)

実験手順

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]+).

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US09440954B2uspto-grants-2016_09