Sulfuric Acid → 21-methylene-20(R)-methylpregn-4-en-3-one

HRID 1107192Notes

Reaction equation

HRID 1107192 reaction equation
CC(C)[O-].[Al+3].CC(C)[O-].CC(C)[O-].[CH2:14]=[CH:15][C@@H:16]([CH3:37])[C@@H:17]1[C@:34]2([CH3:35])[C@H:20]([C@H:21]3[C@H:31]([CH2:32][CH2:33]2)[C@:29]2([CH3:30])[C:24]([CH2:25][C@@H:26]([OH:36])[CH2:27][CH2:28]2)=[CH:23][CH2:22]3)[CH2:19][CH2:18]1.C1(=O)CCCCC1.S(=O)(=O)(O)O>C1(C)C=CC=CC=1.O>[CH2:14]=[CH:15][C@@H:16]([CH3:37])[C@@H:17]1[C@:34]2([CH3:35])[C@H:20]([C@H:21]3[C@H:31]([CH2:32][CH2:33]2)[C@:29]2([CH3:30])[C:24](=[CH:25][C:26](=[O:36])[CH2:27][CH2:28]2)[CH2:23][CH2:22]3)[CH2:19][CH2:18]1

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 7967CyclohexanoneHCID 11143Aluminum isopropoxideHCID 1119825121-methylene-20(R)-methylpregn-5-en-3beta-ol

Product 1

HCID 1542966021-methylene-20(R)-methylpregn-4-en-3-oneYield 74%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 1140TolueneSolvent2×

Procedure

Aluminum isopropoxide (0.39 g, 1.9 mmol) in 3.6 ml of hot toluene was added to a solution of 21-methylene-20(R)-methylpregn-5-en-3β-ol (208.2 mg, 0.6337 mmol) in cyclohexanone (3.6 ml, 35 mmol) and 18 ml of toluene, and the mixture was refluxed with exclusion of moisture for 2 h. After cooling in ice, 0.92 ml of water and 2.2 ml of 3.6 N sulfuric acid were added and the mixture was shaken 1 min. Further water (4.6 ml) was added, the mixture was shaken 5 min., and the aqueous phase was discarded. Volatile components were removed by azeotropic/steam distillation and the resulting aqueous suspension was extracted three times with 5 ml portions of methylene chloride. The combined organic extracts were filtered through a small column of sodium sulfate resting on a bed of diatomaceous earth, all of which was contained in a Pasteur pipette. The residue was washed with 5 ml of methylene chloride and the combined filtrates were concentrated under reduced pressure. Recrystallization of the residual film gave white needles (152.7 mg, 0.4677 mmol, 74%), m.p. 138-139° C. TLC (25% ethyl acetate/hexanes on silica gel) showed a major product at Rf 0.54 with a trace contaminant at Rf 0.71 (starting material Rf 0.36).

Workup

  1. temperaturethe mixture was refluxed with exclusion of moisture for 2 h
  2. temperatureAfter cooling in ice
  3. stirringthe mixture was shaken 5 min.
  4. customVolatile components were removed by azeotropic/steam distillation
  5. extractionthe resulting aqueous suspension was extracted three times with 5 ml portions of methylene chloride
  6. filtrationThe combined organic extracts were filtered through a small column of sodium sulfate resting on a bed of diatomaceous earth
  7. washThe residue was washed with 5 ml of methylene chloride
  8. concentrationthe combined filtrates were concentrated under reduced pressure
  9. customRecrystallization of the residual film

Sources & evidence

ORD record
ord-44c7e859b8ca44c6a527e2a42e93a8ce
Source dataset
uspto-grants-2000_05
Patent number
US06057439

Reaction notes

Loading…