Methanol → Betulonal

HRID 2041883Notes

Reaction equation

HRID 2041883 reaction equation
[CH3:1][C:2]([C@H:4]1[C@@H:8]2[C@@H:9]3[C@@:22]([CH3:25])([CH2:23][CH2:24][C@@:7]2([CH2:31][OH:32])[CH2:6][CH2:5]1)[C@@:21]1([CH3:26])[C@@H:12]([C@:13]2([CH3:30])[C@@H:18]([CH2:19][CH2:20]1)[C:17]([CH3:28])([CH3:27])[C@@H:16]([OH:29])[CH2:15][CH2:14]2)[CH2:11][CH2:10]3)=[CH2:3].CC(C)=O.OS(O)(=O)=O.O=[Cr](=O)=O.CO.O>CC(C)=O>[CH3:3][C:2]([C@H:4]1[C@@H:8]2[C@@H:9]3[C@@:22]([CH3:25])([CH2:23][CH2:24][C@@:7]2([CH:31]=[O:32])[CH2:6][CH2:5]1)[C@@:21]1([CH3:26])[C@@H:12]([C@:13]2([CH3:30])[C@@H:18]([CH2:19][CH2:20]1)[C:17]([CH3:28])([CH3:27])[C:16](=[O:29])[CH2:15][CH2:14]2)[CH2:11][CH2:10]3)=[CH2:1]

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 72326Betulin2×HCID 131709961Jones' reagent

Product 1

HCID 473111BetulonalYield 6%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
0 °C

Procedure

In a 250 ml round-bottomed flask, equipped with a magnetic stirring bar, a 100 ml addition funnel and a septum fitted with a nitrogen inlet, was placed 1 g (2.258 mmol) betulin in 150 ml acetone. The flask was cooled with an ice-acetone bath and the suspension of betulin was treated dropwise with Jones' reagent [L. F. Fieser, M. Fieser, Reagents for Organic Synthesis, vol. 1, 1967, p. 143] over 15 minutes. The reaction mixture was stirred at 0° C. for 2 hours and then treated with methanol (25 ml) until it turned dark green. The reaction mixture was poured onto a mixture of ice and water (50 ml), then acetone and methanol were removed under reduced pressure. The aqueous residue was extracted three times with 40 ml ethyl acetate. The combined organic extracts were washed first with water (20 ml) and then with brine (15 ml), then dried (MgSO4). The solvent was evaporated under reduced pressure to give a white solid. The crude residue was purified by chromatography on silica gel 60G (ethyl acetate/petroleum ether 40-60° C., 1/9 then 1/4) to yield first 59 mg (6%) betulonal as a white solid, then 880 mg (86%) betulonic acid 1 as a white solid.

Workup

  1. customIn a 250 ml round-bottomed flask, equipped with a magnetic stirring bar, a 100 ml addition funnel
  2. customa septum fitted with a nitrogen inlet
  3. temperatureThe flask was cooled with an ice-acetone bath
  4. customacetone and methanol were removed under reduced pressure
  5. extractionThe aqueous residue was extracted three times with 40 ml ethyl acetate
  6. washThe combined organic extracts were washed first with water (20 ml)
  7. dry with materialwith brine (15 ml), then dried (MgSO4)
  8. customThe solvent was evaporated under reduced pressure
  9. customto give a white solid
  10. customThe crude residue was purified by chromatography on silica gel 60G (ethyl acetate/petroleum ether 40-60° C., 1/9

Sources & evidence

ORD record
ord-b5635915052444b4a733f4a7aef54129
Source dataset
uspto-grants-2013_11
Patent number
US08586569B2

Reaction notes

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