Tetrahydrofuran → 21-Desacetoxy-21-Chloro Anecortave

HRID 2198391Notes

Reaction equation

HRID 2198391 reaction equation
ClC(=C1[C@]2(C)[C@H]([C@H]3[C:27](=CC2)[C@:25]2([CH3:26])[C:20](=[CH:21][C:22](=[O:32])[CH2:23][CH2:24]2)CC3)CC1)C(Cl)S(C1C=CC=CC=1)=O.C1C[O:36]CC1.C[O-].[Na+].[Cl:41][CH:42](S(C1C=CC=CC=1)=O)[C:43]([O:64]C)=[C:44]1[C@:61]2([CH3:62])[C@H:47]([C@H:48]3C(=[CH:59][CH2:60]2)[C@]2(C)C(=CC(=O)CC2)[CH2:50][CH2:49]3)[CH2:46][CH2:45]1>CO.O.CC(C)=O>[Cl:41][CH2:42][C:43](=[O:64])[C@:44]1([OH:36])[C@:61]2([CH3:62])[C@H:47]([C@H:48]3[C:27](=[CH:59][CH2:60]2)[C@:25]2([CH3:26])[C:20](=[CH:21][C:22](=[O:32])[CH2:23][CH2:24]2)[CH2:50][CH2:49]3)[CH2:46][CH2:45]1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 10942334Sodium MethoxideHCID 5698509320,21-Dichloro-21-(phenylsulfinyl)pregna-4,9(11),17(20)-trien-3-oneHCID 5701252721-Chloro-20-methoxy-21-(phenylsulfinyl)pregna-4,9(11),17(20)-trien-3-one

Product 1

HCID 1303765421-Desacetoxy-21-Chloro Anecortave

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 887MethanolSolvent2×HCID 962WaterSolvent

Procedure

20,21-Dichloro-21-(phenylsulfinyl)pregna-4,9(11),17(20)-trien-3-one (VII, Example 2, 3.0 g), THF (60 ml), methanol (12 ml) and acetone (9 ml) are cooled to 0° under nitrogen and sodium methoxide in methanol (25%, 2.8 ml) are added. After one hour, by TLC analysis, complete conversion to the 20-methoxy derivative (VIII) had occurred. The resulting mixture is brought to 28° and stirred for 22 hours and then warmed to 30°-35° for five hours. The mixture is diluted with water (150 ml) and then extracted with ethyl acetate-methylene chloride (2×75 ml). The organic extracts are combined, washed with water, dried over sodium sulfate and concentrated under reduced pressure. The concentrate is slurried in methylene chloride (15 ml) and treated with aqueous hydrochloric acid (6 N, 1 ml) at 30°-35° for one hour. The mixture is diluted with methylene chloride (25 ml) and extracted with water (2× 10 ml). The organic layer is separated, dried over sodium sulfate and concentrated under reduced pressure to give the crude product. This material is purified by trituration with hexane/ethyl acetate (7/3, 25 ml) to give the title compound, mp 210.5°-212°; NMR (CDCl3) 0.63, 1.33, 4.47, 5.53 and 5.72δ. ##STR2##

Workup

  1. customis brought to 28°
  2. temperaturewarmed to 30°-35° for five hours
  3. extractionextracted with ethyl acetate-methylene chloride (2×75 ml)
  4. washwashed with water
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. additiontreated with aqueous hydrochloric acid (6 N, 1 ml) at 30°-35° for one hour
  8. additionThe mixture is diluted with methylene chloride (25 ml)
  9. extractionextracted with water (2× 10 ml)
  10. customThe organic layer is separated
  11. dry with materialdried over sodium sulfate
  12. concentrationconcentrated under reduced pressure
  13. customto give the crude product
  14. customThis material is purified by trituration with hexane/ethyl acetate (7/3, 25 ml)

Sources & evidence

ORD record
ord-a2245e0df40142c1b2b8e0239b8b3d4e
Source dataset
uspto-grants-1982_11
Patent number
US04357279

Reaction notes

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