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

HRID 259223

반응식

HRID 259223 반응식
[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+].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]

참가 물질

9

반응물 5

HCID 7918Acetic AnhydrideHCID 24477Sodium ThiosulfateHCID 24524Fluorine2회HCID 517019Sodium Trifluoroacetate2회HCID 705695903beta-Acetoxy-17alpha-hydroxy-16beta-methyl-5alpha-pregnan-20-one

생성물 1

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

시약·촉매·용매 3

HCID 1049Pyridine용매HCID 6212Chloroform용매HCID 6389Trichlorofluoromethane용매

실험 절차

3β-Acetoxy-17α-hydroxy-16β-methyl-5α-pregnan-20-one (1g, 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. 2g) and sodium fluoride (ca. 2g). 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 δ 2.20 (21-Me), 2.00 (3-0.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, 9.13; F, 4.65%).

후처리

  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

출처 및 근거

ORD 기록
ord-341cd432a5774b1abdb3ca24085de1b0
출처 데이터셋
uspto-grants-1977_07
특허 번호
US04036864

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