Reaktion #1172417

ord-ec85956ec6de4fd7bd4275799a2f2d31

Reaktionsgleichung

O=C([O-])O.[Na+]
sodium bicarbonate
COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(C)=O)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.Cl
daunorubicin hydrochloride
COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1
doxorubicin
O=C(O)C(=O)O
oxalic acid
→
COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.Cl
doxorubicin hydrochloride
Ausbeute 80.3%

Edukte

—
14-bromo daunorubicin 13,13-diethoxy ketal
—
solution
O=C([O-])O.[Na+]
sodium bicarbonate
—
XXI
COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(C)=O)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.Cl
daunorubicin hydrochloride
COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1
doxorubicin
O=C(O)C(=O)O
oxalic acid
—
aqueous solution

Reagenzien

Keine

Lösungsmittel

O
water

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Vorschrift

3 g of 14-bromo daunorubicin 13,13-diethoxy ketal, prepared as described in Example 2 from 2.5 g of daunorubicin hydrochloride and isolated by filtration after trituration with a small volume of water, was stirred overnight at 25°-30° C. in 150 ml of a 5% aqueous solution of oxalic acid, at which time hydrolysis of the ketal group was complete. The pH was adjusted to 3.5 using a 5% solution of sodium bicarbonate and then the reaction mixture was kept at 50° C. for 2 days, after which time quantitative HPLC analysis (using the conditions of USP XXI) of the reaction mixture showed the presence of 1.75 g of doxorubicin (as the free substance). Isolation by preparative HPLC using a RP-18 reverse-phase silica gel column gave 1.5 g of doxorubicin hydrochloride having a purity of 98.9%.

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US05008380uspto-grants-1991_04