Sodium Fluoride → 3beta-Acetoxy-9alpha-fluoro-17alpha-hydroxy-16beta-methyl-5alpha-pregnan-20-one

HRID 894506

Reaktionsgleichung

Reaktionsgleichung von HRID 894506
[C:1]([O:4][C@H:5]1[CH2:24][CH2:23][C@@:22]2([CH3:25])[C@@H:7]([CH2:8][CH2:9][C@@H:10]3[C@@H:21]2[CH2:20][CH2:19][C@@:18]2([CH3:26])[C@H:11]3[CH2:12][C@H:13]([CH3:28])[C@:14]2([OH:27])[C:15](=[O:17])[CH3:16])[CH2:6]1)(=[O:3])[CH3:2].C(OC(=O)C)(=O)C.[F:36]C(F)(F)C([O-])=O.[Na+].[F-].[Na+].FF.S([O-])([O-])(=O)=S.[Na+].[Na+]>N1C=CC=CC=1.FC(Cl)(Cl)Cl.C(Cl)(Cl)Cl>[C:1]([O:4][C@H:5]1[CH2:24][CH2:23][C@@:22]2([CH3:25])[C@@H:7]([CH2:8][CH2:9][C@@H:10]3[C@:21]2([F:36])[CH2:20][CH2:19][C@@:18]2([CH3:26])[C@H:11]3[CH2:12][C@H:13]([CH3:28])[C@:14]2([OH:27])[C:15](=[O:17])[CH3:16])[CH2:6]1)(=[O:3])[CH3:2]

Komponenten

10

Edukt 6

HCID 5235Sodium FluorideHCID 7918Acetic AnhydrideHCID 24477Sodium ThiosulfateHCID 24524Fluorine2×HCID 517019Sodium TrifluoroacetateHCID 705695903beta-Acetoxy-17alpha-hydroxy-16beta-methyl-5alpha-pregnan-20-one

Produkt 1

HCID 705714633beta-Acetoxy-9alpha-fluoro-17alpha-hydroxy-16beta-methyl-5alpha-pregnan-20-oneAusbeute 50 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 1049PyridineLösungsmittelHCID 6212ChloroformLösungsmittelHCID 6389TrichlorofluoromethaneLösungsmittel

Versuchsvorschrift

3β-Acetoxy-17α-hydroxy-16β-methyl-5α-pregnan-20-one (1 g, prepared by treatment of the corresponding 3β-ol with acetic anhydride in pyridine) was dissolved in fluorotrichloromethane (250 ml) and chloroform (200 ml) containing sodium trifluoroacetate (ca. 2 g) and sodium fluoride (ca. 2 g). The resulting solution was cooled to -78° and vigourously stirred, whereupon fluorine from four 750 cc bottles (8-10% v/v fluorine in nitrogen) was added over 9-10 hours. The reaction solution was then poured into aqueous sodium thiosulphate and the organic layer was separated, washed with water, dried over potassium carbonate and evaporated to dryness. The residue was purified by liquid chromatography, eluting with cyclohexane containing 30% v/v ethyl acetate and 0.1% v/v pyridine, to yield 3β-acetoxy-9α-fluoro-17α-hydroxy-16β-methyl-5α-pregnan-20-one (50%); m.p. 150° (after recrystallisation from acetone); PMR spectrum includes signals at δ2.20 (21-Me), 2.00 (3-O.CO.CH3), 0.92 (19-Me) and 0.87 (18-Me); FMR φ*+179.5 ppm. (Found: C, 70.51; H, 9.20; F, 4.48; C24H37FO4 requires C, 70.55; H, 9.18, F, 4.65%).

Aufarbeitung

  1. temperatureThe resulting solution was cooled to -78°
  2. additionwas added over 9-10 hours
  3. customthe organic layer was separated
  4. washwashed with water
  5. dry with materialdried over potassium carbonate
  6. customevaporated to dryness
  7. customThe residue was purified by liquid chromatography
  8. washeluting with cyclohexane containing 30% v/v ethyl acetate and 0.1% v/v pyridine

Quellen und Nachweise

ORD-Eintrag
ord-509bb40079154a639c1aa00b93809ced
Quelldatensatz
uspto-grants-1981_08
Patentnummer
US04284558

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