Reaktion #672582

Reaktionsgleichung

NH4OH

trimethylphosphine

1,8-diazabicyclo[5.4.0]undec-7-ene

diphenylphosphoryl azide

NH4Br

NH4OH

epothilone F

→

21-amino epothilone B

Ausbeute 100.3%

Lösungsmittel

EtOAc

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe mixture was stirred for 10 min.
2. 2
   workup.STIRRINGstirred for 6.5 hours
3. 3
   TemperaturThe mixture was cooled to 10° C.
4. 4
   workup.ADDITIONwas added
5. 5
   workup.STIRRINGAfter the mixture was stirred for 5 min
6. 6
   workup.STIRRINGto stir at 35° C. for 4 hours
7. 7
   Temperaturcooled to room temperature
8. 8
   WaschenThe organic layer was washed with aqueous NH4OH (1 M, 20 ml)
9. 9
   ExtraktionThe combined aqueous layers were extracted with EtOAc (20 ml)
10. 10
    WaschenThe combined organic layers were washed with H2O (20 ml)
11. 11
    Trocknendried over MgSO4
12. 12
    SonstigeThe solvents were removed on a rotary evaporator
13. 13
    Sonstigethe residue dried in vacuo

Vorschrift

To a stirred suspension of epothilone F (2.5 g, 4.77 mmol, 86.2% potency) in tetrahydrofuran (25 ml) was added diphenylphosphoryl azide (1.14 ml, 1.45 g, 5.25 mmol, 1.1 equivalents) at room temperature. The mixture was stirred for approximately 5 min. 1,8-diazabicyclo[5.4.0]undec-7-ene (0.86 ml, 0.87 g, 5.73 mmol, 1.2 equivalents) was then added over 10 min. The mixture was stirred for 10 min. and then allowed to warm to 35° C. and stirred for 6.5 hours. The mixture was cooled to 10° C., and a mixture of aqueous solution of NH4Br (2M, 5 ml) and NH4OH (2M, 5 ml) was added. After the mixture was stirred for 5 min, trimethylphosphine (1M in tetrahydrofuran, 5.01 ml, 5.01 mmol, 1.05 equivalents) was added over 10 min at 10° C. The mixture was allowed to stir at 35° C. for 4 hours and then cooled to room temperature. EtOAc (80 ml) and aqueous NH4OH (1 M, 10 ml) were added. The organic layer was washed with aqueous NH4OH (1 M, 20 ml). The combined aqueous layers were extracted with EtOAc (20 ml). The combined organic layers were washed with H2O (20 ml) and dried over MgSO4. The solvents were removed on a rotary evaporator, and the residue dried in vacuo to provide the crude 21-amino epothilone B (2.5 g) as an off-white solid. The crude 21-amino epothilone B (2.45 g) was crystallized from EtOAc/heptane to give 21-amino epothilone B (1.95 g, 90% yield corrected for input potency) as a white solid.

Quelle