Tetrahydrofuran → 21-Chloro-17alpha-hydroxy-20-methoxypregna-4,9(11),20-trien-3-one

HRID 2198389Notes

Reaction equation

HRID 2198389 reaction equation
ClC(=C1[C@]2(C)[C@H]([C@H]3C(=CC2)[C@]2(C)C(=CC(=O)CC2)CC3)CC1)C(Cl)S(C1C=CC=CC=1)=[O:5].C1COCC1.C[O-].[Na+].[Cl:41][CH:42](S(C1C=CC=CC=1)=O)[C:43]([O:64][CH3:65])=[C:44]1[C@:61]2([CH3:62])[C@H:47]([C@H:48]3[C:58](=[CH:59][CH2:60]2)[C@:56]2([CH3:57])[C:51](=[CH:52][C:53](=[O:63])[CH2:54][CH2:55]2)[CH2:50][CH2:49]3)[CH2:46][CH2:45]1>CO.O.CC(C)=O>[Cl:41][CH:42]=[C:43]([O:64][CH3:65])[C@:44]1([OH:5])[C@:61]2([CH3:62])[C@H:47]([C@H:48]3[C:58](=[CH:59][CH2:60]2)[C@:56]2([CH3:57])[C:51](=[CH:52][C:53](=[O:63])[CH2:54][CH2:55]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 8673851121-Chloro-17alpha-hydroxy-20-methoxypregna-4,9(11),20-trien-3-one

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) dry THF (36 ml), methanol (7.5 ml) and acetone (6 ml) are cooled to 0° under nitrogen and sodium methoxide in methanol (25%, 2.8 ml) is added with stirring. After 1 hour of stirring, TLC analysis shows complete conversion of the dichloro starting material (VI) to 21-chloro-20-methoxy-21-(phenylsulfinyl)pregna-4,9(11),17(20)-trien-3-one (VIII, Example 3). The mixture is brought to 20°-25° and stirred for 22 hours and then warmed to 30°-35° for 5 hours. The mixture is diluted with water (100 ml) and 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 triturated with hexane/ethyl acetate (85/15, 25 ml) to give the title compound, mp 197°-199°; NMR (CDCl3) 0.68, 1.35, 3.97, 5.55 and 5.73δ.

Workup

  1. stirringAfter 1 hour of stirring
  2. customis brought to 20°-25°
  3. stirringstirred for 22 hours
  4. temperaturewarmed to 30°-35° for 5 hours
  5. extractionextracted with ethyl acetate-methylene chloride (2×75 ml)
  6. washwashed with water
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe concentrate is triturated with hexane/ethyl acetate (85/15, 25 ml)

Sources & evidence

ORD record
ord-0c8e84e164b243308535186178d65daa
Source dataset
uspto-grants-1982_11
Patent number
US04357279

Reaction notes

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