Acetone → Anecortave Acetate

HRID 65344Notes

Reaction equation

HRID 65344 reaction equation
[OH:1][C@:2]1([C@:28]2([CH3:29])[C@H:14]([C@H:15]3[C:25](=[CH:26][CH2:27]2)[C@:23]2([CH3:24])[C:18](=[CH:19][C:20](=[O:30])[CH2:21][CH2:22]2)[CH2:17][CH2:16]3)[CH2:13][CH2:12]1)[C:3]([O:5]C1C=CC=CC=1)=[CH2:4].P([O-])([O-])([O-])=O.[K+].[K+].[K+].OOS([O-])=O.[K+].[OH-:45].[K+].C[C:48]([CH3:50])=[O:49]>O.C1(C)C=CC=CC=1.C(Cl)Cl>[OH:1][C@:2]1([C@:28]2([CH3:29])[C@H:14]([C@H:15]3[C:25](=[CH:26][CH2:27]2)[C@:23]2([CH3:24])[C:18](=[CH:19][C:20](=[O:30])[CH2:21][CH2:22]2)[CH2:17][CH2:16]3)[CH2:13][CH2:12]1)[C:3](=[O:4])[CH2:5][O:49][C:48](=[O:45])[CH3:50]

Participants

8

Reactant 5

HCID 180Acetone2×HCID 14797Potassium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 1382382517alpha-Hydroxy-20-phenoxypregna-4,9(11),20-trien-3-oneHCID 23707502Potassium hydroxy sulfite

Product 1

HCID 111332Anecortave Acetate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21877217Toluene methylene chlorideSolvent

Conditions

Temperature
15 °C

Procedure

17α-hydroxy-20-phenoxypregna-4,9(11),20-trien-3-one (4.05 grams, 10 mmoles) is slurried with 210 ml of an aqueous pH 8 potassium phosphate buffer (0.5M in PO4 ≡), 20 ml of acetone, 40 ml of toluene/methylene chloride (3:2) and n-tetrabutylammonium bromide is (0.645 grams, 2.0 mmole) added. The pH is adjusted to 7.0 to 8.0 and the mixture cooled to 15° C. and an OXONE® solution is (18.4 gms, 30 mmoles dissolved in 65 ml of water) added dropwise by an addition funnel while stirring and maintaining pH at 7.0 to 8.0 by addition of a 30% potassium hydroxide solution. The reaction is worked up by separating the layers and replacing the organic solvent with toluene to a volume of 100 ml so as to remove water. After cooling to 10° C., 3 ml of glacial acetic acid is added. The product is isolated by replacing the toluene with acetone and filtering to obtain 3.12 g of 17α-hydroxy-21-acetoxypregna-4,9(11)-diene-3,20-dione.

Workup

  1. additionadded
  2. additionadded dropwise by an addition funnel
  3. temperaturemaintaining pH at 7.0 to 8.0
  4. customby separating the layers
  5. customto remove water
  6. temperatureAfter cooling to 10° C.
  7. addition3 ml of glacial acetic acid is added
  8. customThe product is isolated
  9. filtrationfiltering

Sources & evidence

ORD record
ord-a9ec3ad44eae4e0c8fd779ec69e81f7c
Source dataset
uspto-grants-1986_09
Patent number
US04613463

Reaction notes

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