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

HRID 894506

Reaction equation

HRID 894506 reaction equation
[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]

Participants

10

Reactant 6

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6212ChloroformSolventHCID 6389TrichlorofluoromethaneSolvent

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-509bb40079154a639c1aa00b93809ced
Source dataset
uspto-grants-1981_08
Patent number
US04284558

Linked notes

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