Hydrochloric Acid → (-)-4'-Demethylepipodophyllotoxin

HRID 613775Notes

Reaction equation

HRID 613775 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C@H:13]2[C@H:22]3[C:23]([O:25][CH2:26][C@@H:21]3[C@@H:20]([OH:27])[C:19]3[CH:18]=[C:17]4[O:28][CH2:29][O:30][C:16]4=[CH:15][C:14]2=3)=[O:24])[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9]C.Cl>C(Cl)Cl.C(OCC)C>[CH3:12][O:11][C:7]1[CH:6]=[C:5]([C@H:13]2[C@H:22]3[C:23]([O:25][CH2:26][C@@H:21]3[C@H:20]([OH:27])[C:19]3[CH:18]=[C:17]4[O:28][CH2:29][O:30][C:16]4=[CH:15][C:14]2=3)=[O:24])[CH:4]=[C:3]([O:2][CH3:1])[C:8]=1[OH:9]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 10607Podophyllotoxin

Product 1

HCID 122797(-)-4'-Demethylepipodophyllotoxin

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

1 g of podophyllotoxin I is dissolved in a mixture of 15 ml of CH2Cl2 and 5 ml of ethyl ether. A slight stream of gaseous hydrochloric acid is introduced into the solution for 15 min at -10° C. and then stirring is maintained at this temperature for 1 h. After evaporating the reaction mixture without heating, 0.54 g of D,L-methionine and then 5 ml of methanesulfonic acid are added. After dissolving and stirring for 1 h with return to ordinary temperature, the reaction mixture is plunged into a water-acetone mixture and then BaCO3 is added to neutrality. After extracting with ethyl acetate, separating by settling, drying over Na2SO4, filtering and evaporating under reduced pressure, a residue is obtained which is crystallized from ethyl ether to provide 0.5 g (Yd 52%) of white crystals of 4'-demethylepipodophyllotoxin exhibiting a homogeneous spot by TLC.

Workup

  1. temperatureis maintained at this temperature for 1 h
  2. customAfter evaporating the reaction mixture
  3. temperaturewithout heating
  4. addition0.54 g of D,L-methionine and then 5 ml of methanesulfonic acid are added
  5. dissolutionAfter dissolving
  6. stirringstirring for 1 h with return to ordinary temperature
  7. additionBaCO3 is added to neutrality
  8. extractionAfter extracting with ethyl acetate
  9. customseparating
  10. dry with materialdrying over Na2SO4
  11. filtrationfiltering
  12. customevaporating under reduced pressure
  13. customa residue is obtained which
  14. customis crystallized from ethyl ether

Sources & evidence

ORD record
ord-d4caf1967a024645a3c2eda5724790e0
Source dataset
uspto-grants-1999_12
Patent number
US06008382

Reaction notes

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