Реакция #60576

ord-f29323239000469cbfcf960cb7b57b7e

Уравнение реакции

COc1cc2c(cc1O)CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](O)CC[C@@H]12
2-methoxy-estra-1,3,5(10)-triene-3,17β-diol
CCN(CC)S(F)(F)F
diethylamino sulfur trifluoride
→
COc1cc2c(cc1O)CC[C@@H]1[C@@H]2CC[C@]2(C)[C@H](F)CC[C@@H]12
17α-fluoro-3-hydroxy-2-methoxy-estra-1,3,5(10)-triene
Выход 21.0%

Реактанты

COc1cc2c(cc1O)CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](O)CC[C@@H]12
2-methoxy-estra-1,3,5(10)-triene-3,17β-diol
CCN(CC)S(F)(F)F
diethylamino sulfur trifluoride

Реагенты

Нет

Растворители

ClCCl
dichloromethane

Условия реакции

Температура
-35°CELSIUS
Подробные условия
See reaction.notes.procedure_details.

Обработка

  1. 1
    Другоеthe cold bath was removed
  2. 2
    workup.ADDITIONit was poured into aqueous sodium bicarbonate solution
  3. 3
    Экстракцияextracted with dichloromethane (3×)
  4. 4
    ДругоеThe combined organic phases were dried
  5. 5
    Концентрированиеconcentrated by evaporation in a rotary evaporator
  6. 6
    ДругоеFlash chromatography (cyclohexane/ethyl acetate=10:1) yielded 49% crude product, which
  7. 7
    Другоеwas purified by means of HPLC (Chiracel OD-H 250×4.6 mm; n-heptane/2-propanol=95/5)

Методика

215 mg of 2-methoxy-estra-1,3,5(10)-triene-3,17β-diol was dissolved in 20 ml of absolute dichloromethane and cooled to −35° C. Then, 280 μl of diethylamino sulfur trifluoride was added, and the cold bath was removed. After 1 hour, it was poured into aqueous sodium bicarbonate solution and extracted with dichloromethane (3×). The combined organic phases were dried and concentrated by evaporation in a rotary evaporator. Flash chromatography (cyclohexane/ethyl acetate=10:1) yielded 49% crude product, which was purified by means of HPLC (Chiracel OD-H 250×4.6 mm; n-heptane/2-propanol=95/5). 46 mg (21%) of 17α-fluoro-3-hydroxy-2-methoxy-estra-1,3,5(10)-triene was obtained as colorless crystals.

Источник

DOI: 10.6084/m9.figshare.5104873.v1Патент: US07427610B2uspto-grants-2008_09