Reaction #531849

ord-078f2edd839a40679aec2e755b2e5306

Reaction equation

C=C1C[C@@H]2[C@H](CC[C@]3(C)C(=O)CC[C@@H]23)[C@@]2(C)C=CC(=O)C=C12
exemestane
[BH4-].[Na+]
NaBH4
C=C1C[C@@H]2[C@H](CC[C@]3(C)C(=O)CC[C@@H]23)[C@@]2(C)C=CC(=O)C=C12
exemestane
C=C1C[C@@H]2[C@H](CC[C@]3(C)C(=O)CC[C@@H]23)[C@@]2(C)C=CC(=O)C=C12
exemestane
[BH4-].[Na+]
NaBH4
C=C1C[C@@H]2[C@H](CC[C@]3(C)C(=O)CC[C@@H]23)[C@@]2(C)C=CC(=O)C=C12
exemestane
→
C=C1C[C@@H]2[C@H](CC[C@]3(C)C(O)CC[C@@H]23)[C@@]2(C)C=CC(=O)C=C12
17-dihydroexemestane

Reactants

C=C1C[C@@H]2[C@H](CC[C@]3(C)C(=O)CC[C@@H]23)[C@@]2(C)C=CC(=O)C=C12
exemestane
[BH4-].[Na+]
NaBH4
C=C1C[C@@H]2[C@H](CC[C@]3(C)C(=O)CC[C@@H]23)[C@@]2(C)C=CC(=O)C=C12
exemestane
C=C1C[C@@H]2[C@H](CC[C@]3(C)C(=O)CC[C@@H]23)[C@@]2(C)C=CC(=O)C=C12
exemestane
[BH4-].[Na+]
NaBH4
C=C1C[C@@H]2[C@H](CC[C@]3(C)C(=O)CC[C@@H]23)[C@@]2(C)C=CC(=O)C=C12
exemestane

Reagents

None

Solvents

CO.O
methanol water

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    workup.WAITThe mixture is left at ambient temperature for at least 1 h
  2. 2
    Otherreaction completeness
  3. 3
    Otherto solvent removal by vacuum
  4. 4
    workup.DISSOLUTIONAfter dissolving the dry residue in 1.5M HCl
  5. 5
    workup.ADDITION1M KOH (500 μL) is added
  6. 6
    ExtractionThe mixture is extracted by ethyl ether
  7. 7
    Otherdried by vacuum
  8. 8
    workup.DISSOLUTIONre-dissolved in 30 ml ethyl ether:hexane (1:1) at 50° C
  9. 9
    Washthe formed crystals are washed with hexane
  10. 10
    Otherdried by vacuum
  11. 11
    Otherresulting in a clear peak at m/z 299 [M]+

Procedure

17-dihydroexemestane is prepared from exemestane as described in Mareck, U. et al., Rapid Commun Mass Spectrom, 20: 1954-62, 2006 with minor modifications. Briefly, exemestane and NaBH4 are individually dissolved in methanol/water (4:1, v/v). For reduction of the 17-keto functional group of exemestane, NaBH4 is slowly added to the suspended exemestane in a 1:2 molar ratio. The mixture is left at ambient temperature for at least 1 h and then assayed by thin layer chromatography to ensure reaction completeness prior to solvent removal by vacuum. After dissolving the dry residue in 1.5M HCl, 1M KOH (500 μL) is added. The mixture is extracted by ethyl ether, dried by vacuum, and re-dissolved in 30 ml ethyl ether:hexane (1:1) at 50° C. After 3 days, the formed crystals are washed with hexane and dried by vacuum. The synthesized 17-dihydroexemestane structure is characterized by a Bruker 500 MHz nuclear magnetic resonance (NMR) spectrometer and HPLC/MS/MS, with the MS spectrum resulting in a clear peak at m/z 299 [M]+ and a daughter product at m/z 135.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08476023B2uspto-grants-2013_07