Ethanol → Colestolone

HRID 330585Notes

Reaction equation

HRID 330585 reaction equation
C([O:9][C@H:10]1[CH2:34][CH2:33][C@@:32]2([CH3:35])[C@@H:12]([CH2:13][CH:14]=[C:15]3[C@@H:31]2[CH2:30][CH2:29][C@@:28]2([CH3:36])[C@@:16]43[O:37][C@H:17]4[CH2:18][C@@H:19]2[C@H:20]([CH3:27])[CH2:21][CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])[CH2:11]1)(=O)C1C=CC=CC=1.C(O)C.O.OS(O)(=O)=O>CCCCCC>[OH:9][C@H:10]1[CH2:34][CH2:33][C@@:32]2([CH3:35])[C@@H:12]([CH2:13][CH2:14][C:15]3[C@@H:31]2[CH2:30][CH2:29][C@@:28]2([CH3:36])[C:16]=3[C:17](=[O:37])[CH2:18][C@@H:19]2[C@H:20]([CH3:27])[CH2:21][CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])[CH2:11]1

Participants

6

Reactant 4

HCID 702EthanolHCID 962WaterHCID 1118Sulfuric AcidHCID 14696446HCID 14696446, compound

Product 1

HCID 10046567Colestolone

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Conditions

Temperature
5 °C

Procedure

A mixture of 120 g (0.238 mol) of 5, 3.0 liters of 95% ethanol, and 350 mL of water in a 5 liter round bottom flask is cooled to 5° C. in an ice bath for 30 minutes. Concentrated H2SO4 (650 mL) is added to this mixture over a period of 10 minutes in 50 mL portions. Any large chunks of suspended material are broken up mechanically. The mixture is heated under reflux for 20-24 hours. The brownish reaction mixture is cooled to 20° C. using an ice bath and then poured into 7 Kg of ice in a 12 liter carboy. The paste-like precipitate is collected on a Buchner funnel using either polypropylene filter cloth (Aldrich) or three layers of Whatman #1 filter paper, which is occasionally scratched to facilitate filtration. The pale-yellow cake is washed three times with 1 liter of cold water and dissolved in 1 liter of hot methanol, to which 1 liter of hexane and 50 mL of hot water are added. The resulting two-phase system is heated on a steam bath until all solid material is dissolved. This mixture is allowed to cool for 2-3 hours to 20° C.; at this point crystals begin to form at the solvent interface. The mixture is then cooled overnight at -15° C. to give a brown upper hexane phase, a lower light yellow aqueous phase, and white crystalline material. The crystals (roughly 90% pure by TLC) are collected by suction filtration and recrystallized again from methanol/hexane/water (2:2:1) as described above.

Workup

  1. temperatureThe mixture is heated
  2. temperatureunder reflux for 20-24 hours
  3. customThe brownish reaction mixture
  4. temperatureis cooled to 20° C.
  5. customThe paste-like precipitate is collected on a Buchner funnel
  6. filtrationfilter cloth (Aldrich) or three layers of Whatman #1
  7. filtrationfilter paper, which
  8. filtrationfiltration
  9. washThe pale-yellow cake is washed three times with 1 liter of cold water
  10. dissolutiondissolved in 1 liter of hot methanol, to which 1 liter of hexane and 50 mL of hot water
  11. additionare added
  12. temperatureThe resulting two-phase system is heated on a steam bath until all solid material
  13. dissolutionis dissolved
  14. temperatureto cool for 2-3 hours to 20° C.
  15. customto form at the solvent interface
  16. temperatureThe mixture is then cooled overnight at -15° C.
  17. filtrationThe crystals (roughly 90% pure by TLC) are collected by suction filtration
  18. customrecrystallized again from methanol/hexane/water (2:2:1)

Sources & evidence

ORD record
ord-8f8e648ea0fb4429b84be28553edbc98
Source dataset
uspto-grants-1990_01
Patent number
US04897475

Reaction notes

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