Реакция #88027

ord-a4e95bd6a3984fc58b661a90852fe3e1

Уравнение реакции

CC(C)(C)OC(=O)c1ccc(NS(C)(=O)=O)s1
tert-butyl 5-(methylsulfonamido)thiophene-2-carboxylate
Cl.ClCCN1CCOCC1
4-(2-chloroethyl)morpholine hydrochloride
O=C([O-])[O-].[K+].[K+]
K2CO3
CC(C)(C)OC(=O)c1ccc(N(S(C)(=O)=O)S(C)(=O)=O)s1
tert-butyl 5-(N-(methylsulfonyl)methylsulfonamido)thiophene-2-carboxylate
Cl.ClCCN1CCOCC1
4-(2-chloroethyl)morpholine hydrochloride
O=C([O-])[O-].[K+].[K+]
K2CO3
CC(C)(C)OC(=O)c1ccc(N(CCN2CCOCC2)S(C)(=O)=O)s1
tert-butyl 5-(N-(2-morpholinoethyl)methylsulfonamido)-thiophene-2-carboxylate
Выход 119.4%

Растворители

Условия реакции

Температура
80°CELSIUS
Подробные условия
See reaction.notes.procedure_details.

Обработка

  1. 1
    Температураwas heated to 80° C. for 4 hours
  2. 2
    Температураheated to 80° C. for additional 2 hours
  3. 3
    ДругоеThe two reaction mixtures
  4. 4
    Другоеpartitioned between EtOAc and water
  5. 5
    ЭкстракцияThe aqueous phase was extracted with EtOAc
  6. 6
    Промывкаthe combined organic layers were washed several times with brine
  7. 7
    Сушкаdried over sodium sulfate
  8. 8
    Фильтрацияfiltered
  9. 9
    Концентрированиеconcentrated to dryness
  10. 10
    ДругоеThe residue was purified by flash chromatography on silica gel (petroleum ether/EtOAc=6/4 to EtOAc 100%)

Методика

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]+).

Источник

DOI: 10.6084/m9.figshare.5104873.v1Патент: US09440954B2uspto-grants-2016_09