Reaction #60577

ord-945a3c1ebec748c38b72cfaab591509c

Reaction equation

COc1cc2c(cc1OS(N)(=O)=O)CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
2-methoxy-17-oxo-estra-1,3,5(10)-trien-3-yl sulfamate
Cl.NO
hydroxylamine hydrochloride
O=C([O-])O.[Na+]
sodium bicarbonate
O
water
→
COc1cc2c(cc1OS(N)(=O)=O)CC[C@@H]1[C@@H]2CC[C@]2(C)/C(=N/O)CC[C@@H]12
2-methoxy-(E)-17-(oximino)-estra-1,3,5(10)-trien-3-yl sulfamate
Yield 74.9%
COc1cc2c(cc1OS(N)(=O)=O)CC[C@@H]1[C@@H]2CC[C@]2(C)/C(=N/O)CC[C@@H]12
2-Methoxy-(E)-17-(oximino)-estra-1,3,5(10)-trien-3-yl Sulfamate
Yield 74.9%

Reactants

COc1cc2c(cc1OS(N)(=O)=O)CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
2-methoxy-17-oxo-estra-1,3,5(10)-trien-3-yl sulfamate
Cl.NO
hydroxylamine hydrochloride
O=C([O-])O.[Na+]
sodium bicarbonate
O
water

Reagents

None

Solvents

CO
methanol
CCOC(C)=O
ethyl acetate

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    Temperatureunder reflux for one hour
  2. 2
    OtherAfter phase separation
  3. 3
    Extractionthe aqueous phase was extracted twice more with 15 ml each of ethyl acetate
  4. 4
    WashThe combined organic phases were first washed with 15 ml of 0.5N HCl
  5. 5
    Dryingwith saturated NaCl solution, dried on sodium sulfate
  6. 6
    Concentrationconcentrated by evaporation in a rotary evaporator
  7. 7
    OtherThe crude product was purified by flash chromatography (toluene/ethyl acetate 3:1)

Procedure

A suspension of 570 mg of 2-methoxy-17-oxo-estra-1,3,5(10)-trien-3-yl sulfamate, 365 mg of hydroxylamine hydrochloride and 441 mg of sodium bicarbonate in 8 ml of methanol was stirred under reflux for one hour. Then, it was mixed with 30 ml each of water and ethyl acetate. After phase separation, the aqueous phase was extracted twice more with 15 ml each of ethyl acetate. The combined organic phases were first washed with 15 ml of 0.5N HCl and then with saturated NaCl solution, dried on sodium sulfate and concentrated by evaporation in a rotary evaporator. The crude product was purified by flash chromatography (toluene/ethyl acetate 3:1). 444 mg (73%) of 2-methoxy-(E)-17-(oximino)-estra-1,3,5(10)-trien-3-yl sulfamate (17) was obtained as colorless crystals.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07427610B2uspto-grants-2008_09