Methanol → 17alpha-Hydroxy-6,16-dimethylenepregna-4-ene-3,20-dione

HRID 370419Notes

Reaction equation

HRID 370419 reaction equation
[CH2:1]=[C:2]1[C:21]2[C@:16]([CH3:23])([CH2:17][CH2:18][C:19](=[O:22])[CH:20]=2)[C@@H:15]2[C@H:4]([C@H:5]3[C@:12]([CH3:24])([CH2:13][CH2:14]2)[C:8](C(=O)C)=[C:7](CS(C2C=CC=CC=2)=O)[CH2:6]3)[CH2:3]1.[C:34]1([CH3:40])C=CC=CC=1.[CH3:41][OH:42].C[O:44]P(OC)OC>C(OCC)(=O)C.O>[OH:42][C@:41]1([C@:12]2([CH3:24])[C@H:5]([C@H:4]3[C@H:15]([CH2:14][CH2:13]2)[C@:16]2([CH3:23])[C:21](=[CH:20][C:19](=[O:22])[CH2:18][CH2:17]2)[C:2](=[CH2:1])[CH2:3]3)[CH2:6][C:7]1=[CH2:8])[C:34](=[O:44])[CH3:40]

Participants

7

Reactant 4

HCID 887MethanolHCID 1140TolueneHCID 8472Trimethyl phosphiteHCID 137303406-Methylene-16-(phenylsulfinylmethyl)pregna-4,16-diene-3,20-dione

Product 1

HCID 1331493217alpha-Hydroxy-6,16-dimethylenepregna-4-ene-3,20-dione

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

6-Methylene-16-phenylsulfonylmethylpregna-4,16-diene-3,20-dione (Example 8, 2.0 g) is placed in a 30-ml vial under nitrogen. Toluene (20 ml), methanol (2.89 ml), TEA (0.181 ml) and trimethylphosphite 1.02 ml) are added. After 1 hr at 20°-25°, the sealed vial was plunged into a hot oil bath with a bath temperature of 90° which is stirred at 90° for 4 hrs, at which time TLC shows the reaction to be essentially complete. The reaction mixture is transferred to a separatory funnel and water (10 ml) is added. Ethyl acetate (10 ml) is added to the organic mixture, which is washed with water (2×10 ml). The aqueous portion is back-extracted with toluene/ethyl acetate: 1/1. After the phases are separated, the organic phase is filtered through sodium sulfate and the filtrate is concentrated under reduced pressure to a volume of about 8 ml. This concentrate is permitted to sit at 20°-25° for approximately 1/2 hr. The resulting crystals are washed down into a flask with toluene (2 ml) and cooled to 5° for 2 hrs, then to -20° for 48 hrs. The crystals were collected with toluene (-20°), then with hexane three times and dried under nitrogen to yield the title compound.

Workup

  1. customthe sealed vial was plunged into a hot oil bath with a bath
  2. customthe reaction
  3. customThe reaction mixture is transferred to a separatory funnel
  4. washis washed with water (2×10 ml)
  5. extractionThe aqueous portion is back-extracted with toluene/ethyl acetate
  6. customAfter the phases are separated
  7. filtrationthe organic phase is filtered through sodium sulfate
  8. concentrationthe filtrate is concentrated under reduced pressure to a volume of about 8 ml
  9. waitto sit at 20°-25° for approximately 1/2 hr
  10. washThe resulting crystals are washed down into a flask with toluene (2 ml)
  11. temperaturecooled to 5° for 2 hrs
  12. waitto -20° for 48 hrs
  13. customThe crystals were collected with toluene (-20°)
  14. dry with materialwith hexane three times and dried under nitrogen

Sources & evidence

ORD record
ord-297a3a8dd35a43158fd02b1ff4a44083
Source dataset
uspto-grants-1985_07
Patent number
US04526720

Reaction notes

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