Water → Almestrone

HRID 352309Notes

Reaction equation

HRID 352309 reaction equation
[CH3:1][C@@H:2]1[CH2:19][C:18]2[C@:13](C)([CH2:14][CH2:15][C:16](=[O:20])[CH:17]=2)[C@@H:12]2[C@@H:3]1[C@H:4]1[C@@:8]([CH2:10][CH2:11]2)([CH3:9])[C:7](=[O:22])[CH2:6][CH2:5]1.O>C(O)(=O)C>[CH3:1][C@H:2]1[C@H:3]2[C@H:4]3[C@:8]([CH3:9])([CH2:10][CH2:11][C@@H:12]2[C:13]2[CH:14]=[CH:15][C:16]([OH:20])=[CH:17][C:18]=2[CH2:19]1)[C:7](=[O:22])[CH2:6][CH2:5]3

Participants

4

Reactant 2

HCID 962WaterHCID 23383196HCID 23383196, compound

Product 1

HCID 65601AlmestroneYield 82%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 114 g of 7α-methylandrost-4-ene-3,17-dione 45a in 1,500 mL of glacial acetic acid was added 106 g of CuCl2. The mixture with stirring was heated to 60° C. for 72 h. The reaction mixture was poured into H2O (500 mL reaction mixture to 3,500 mL H2O) and the precipitate collected by filtration and air dried for 18 h. The solid was dissolved in methylene chloride (2 L) and washed with sat. NaHCO3 (2 L), H2O (2 L), and sat. NaCl (2 L). The methylene chloride solution was dried over MgSO4, and filtered. The methylene chloride solution was filtered (suction chromatography) through 1.5 kg of flash chromatography silica gel 60 (230-400 mesh). The pad of silica gel was further eluted with additional MeCl2. The MeCl2 solutions were combined and then treated with Norite, filtered through a pad of celite and then after evaporation at reduced pressure there was obtained 91.3 g of pure 13 (82%).

Workup

  1. filtrationthe precipitate collected by filtration and air
  2. customdried for 18 h
  3. dissolutionThe solid was dissolved in methylene chloride (2 L)
  4. washwashed with sat. NaHCO3 (2 L), H2O (2 L), and sat. NaCl (2 L)
  5. dry with materialThe methylene chloride solution was dried over MgSO4
  6. filtrationfiltered
  7. filtrationThe methylene chloride solution was filtered (suction chromatography) through 1.5 kg of flash chromatography silica gel 60 (230-400 mesh)
  8. washThe pad of silica gel was further eluted with additional MeCl2
  9. additiontreated with Norite
  10. filtrationfiltered through a pad of celite
  11. customafter evaporation at reduced pressure

Sources & evidence

ORD record
ord-28e989b979f94f32a2d0b1f81aebbaf0
Source dataset
uspto-grants-2004_06
Patent number
US06747018B2

Reaction notes

Loading…