Citric Acid → Estradiol sulfamate

HRID 1831861Notes

Reaction equation

HRID 1831861 reaction equation
[S:1](=[O:24])(=[O:23])([O:3][C:4]1[CH:21]=[CH:20][C:19]2[C@@H:18]3[C@H:9]([C@H:10]4[C@@:14]([CH2:16][CH2:17]3)([CH3:15])[C:13](=[O:22])[CH2:12][CH2:11]4)[CH2:8][CH2:7][C:6]=2[CH:5]=1)[NH2:2].[BH4-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(O)C.O>[S:1](=[O:23])(=[O:24])([O:3][C:4]1[CH:21]=[CH:20][C:19]2[C@@H:18]3[C@H:9]([C@H:10]4[C@@:14]([CH2:16][CH2:17]3)([CH3:15])[C@@H:13]([OH:22])[CH2:12][CH2:11]4)[CH2:8][CH2:7][C:6]=2[CH:5]=1)[NH2:2]

Participants

6

Reactant 3

HCID 311Citric AcidHCID 127676Estrone sulfamateHCID 4311764Sodium borohydride

Product 1

HCID 6918339Estradiol sulfamate

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent3×

Conditions

Temperature
3.5 °C

Procedure

To a cold (2-5° C.) suspension of moist 17-Oxoestra-1,3,5(10)-trien-3-yl sulfamate (171.7 mmol, from procedure I) in ethanol (450 ml), a solution of sodium borohydride (156.23 mmol) in water (94 ml) was added at 2-5° C. within a period of 20 minutes. The resulting mixture was stirred at 2-5° C. for another 20 hours. A solution of citric acid (495.86 mmol) in water (668 ml) was then added at this temperature within a period of 15 minutes to adjust the pH to 3. Water (668 ml) was added. The resulting crystalline solid was filtered and washed three times with water (500 ml). The wet crystals were suspended in acetone (2010 ml) and the resulting suspension was heated under reflux until complete dissolution. Removal of acetone (1700 ml) by destination resulted in a suspension, which was cooled to ambient temperature and filtered. The crystalline solid was washed with cold acetone (50 ml) and dried in vacuum. Yield: 45.06 g white crystals, purity (HPLC): 99.61%.

Workup

  1. filtrationThe resulting crystalline solid was filtered
  2. washwashed three times with water (500 ml)
  3. temperaturethe resulting suspension was heated
  4. temperatureunder reflux until complete dissolution
  5. customRemoval of acetone (1700 ml) by destination
  6. customresulted in a suspension, which
  7. temperaturewas cooled to ambient temperature
  8. filtrationfiltered
  9. washThe crystalline solid was washed with cold acetone (50 ml)
  10. customdried in vacuum

Sources & evidence

ORD record
ord-717cd3dc2c0249818bdd38897f5d9247
Source dataset
uspto-grants-2006_06
Patent number
US07067683B2

Reaction notes

Loading…