Dexamethasone → 9-Fluoro-11,17,21-trihydroxy-16-methylpregn-4-ene-3,20-dione

HRID 2197392Notes

Reaction equation

HRID 2197392 reaction equation
[CH3:1][C@H:2]1[C@:19]([OH:24])([C:20]([CH2:22][OH:23])=[O:21])[C@:18]2([CH3:25])[C@H:4]([C@H:5]3[C@:15]([F:27])([C@@H:16]([OH:26])[CH2:17]2)[C@:14]2([CH3:28])[C:8](=[CH:9][C:10]([CH:12]=[CH:13]2)=[O:11])[CH2:7][CH2:6]3)[CH2:3]1.[H][H]>CCOC(C)=O.C(O)C.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Rh]>[F:27][C@@:15]12[C@:14]3([CH3:28])[C:8](=[CH:9][C:10](=[O:11])[CH2:12][CH2:13]3)[CH2:7][CH2:6][C@H:5]1[C@H:4]1[C@@:18]([CH3:25])([C@@:19]([OH:24])([C:20](=[O:21])[CH2:22][OH:23])[C@H:2]([CH3:1])[CH2:3]1)[CH2:17][C@@H:16]2[OH:26]

Participants

7

Reactant 2

HCID 5743DexamethasoneHCID 178418361HCID 178418361, compound

Product 1

HCID 227925479-Fluoro-11,17,21-trihydroxy-16-methylpregn-4-ene-3,20-dioneYield 95.5%

Reagents, catalysts & solvents 4

HCID 84599Chlorotris(triphenylphosphine)rhodium(I)CatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a 1000 mL round-bottomed flask was suspended dexamethasone (10 g, 25.48 mmol) in EtOAc (400 mL) and ethanol (100 mL) and tris(triphenylphosphine)rhodium(I)chloride (Wilkinson's catalyst, 2.5 g, 2.70 mmol) was added together with a magnetic stirrer bar. The mixture was vigorously stirred in a hydrogen atmosphere (1 atm) at room temperature for 1 week and another 1.0 g of the catalyst was added. The reaction was allowed to proceed for another week and the resulting mixture was concentrated in vacuo to obtain a solid that was suspended in DCM (100 ml) and the suspension was filtered. The obtained solid was washed with 3 portions of DCM (50 ml) and dried on the sinter in air, yielding 9.6 g of the target compound as an off white solid. APCI-MS m/z: 395 [MH+].

Workup

  1. customIn a 1000 mL round-bottomed flask was suspended
  2. waitto proceed for another week
  3. concentrationthe resulting mixture was concentrated in vacuo
  4. customto obtain a solid
  5. filtrationthe suspension was filtered
  6. washThe obtained solid was washed with 3 portions of DCM (50 ml)
  7. customdried on the sinter in air

Sources & evidence

ORD record
ord-3cdb4df603b6487da258feee23b51e77
Source dataset
uspto-grants-2012_12
Patent number
US08338587B2

Reaction notes

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