2,2-Dimethoxypropane → Androsta-3,5,16-trien-3-yl Methyl Ether

HRID 1953496Notes

Reaction equation

HRID 1953496 reaction equation
[CH3:1][C@:2]12[CH2:19][CH2:18][C@H:17]3[C@@H:7]([CH2:8][CH2:9][C:10]4[C@:15]3([CH3:16])[CH2:14][CH2:13][C:12](=[O:20])[CH:11]=4)[C@@H:6]1[CH2:5][CH:4]=[CH:3]2.[CH3:21]OC(OC)(C)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>CO.CN(C=O)C>[CH3:21][O:20][C:12]1[CH2:13][CH2:14][C@@:15]2([CH3:16])[C:10](=[CH:9][CH2:8][C@@H:7]3[C@@H:17]2[CH2:18][CH2:19][C@@:2]2([CH3:1])[C@H:6]3[CH2:5][CH:4]=[CH:3]2)[CH:11]=1

Participants

7

Reactant 4

HCID 64952,2-DimethoxypropaneHCID 92979Androsta-4,16-dien-3-oneHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 15858921Androsta-3,5,16-trien-3-yl Methyl Ether

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a partial solution of androsta-4,16-dien-3-one (1.00 g, 3.70 mmol) in 2.2 dimethoxypropane (5.0 ml, 41 mmol) and 5 ml DMF were added methanol (0.2 ml) and p-toluenesulfonic acid monohydrate (26.4 mg, 0.139 mmol). The mixture was refluxed 5 h, after which it was cooled and sodium bicarbonate (152.5 mg) was added. The suspension was partitioned between 50 ml of ice water and 50 ml of ethyl acetate. The organic layer was washed with two 50 ml portions of water+50 ml of brine, dried over 20 magnesium sulfate, filtered, and concentrated under reduced pressure. The residual oil was taken up in 50 ml of hot hexane and filtered through a 12 mm×30 mm column of silica gel 60 using 150 ml of hot hexane. The combined filtrates were concentrated under reduced pressure and recrystallized from acetone/methanol to give white crystals (468.0 mg, 1.645 mmol, 446), m.p. 83-92° C.

Workup

  1. temperatureThe mixture was refluxed 5 h
  2. temperatureafter which it was cooled
  3. customThe suspension was partitioned between 50 ml of ice water and 50 ml of ethyl acetate
  4. washThe organic layer was washed with two 50 ml portions of water+50 ml of brine
  5. dry with materialdried over 20 magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. filtrationfiltered through a 12 mm×30 mm column of silica gel 60 using 150 ml of hot hexane
  9. concentrationThe combined filtrates were concentrated under reduced pressure
  10. customrecrystallized from acetone/methanol
  11. customto give white crystals (468.0 mg, 1.645 mmol, 446), m.p. 83-92° C.

Sources & evidence

ORD record
ord-659508ded6a64f899d10462276c74175
Source dataset
uspto-grants-2000_09
Patent number
US06117860

Reaction notes

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