Reaktion #1012640

Reaktionsgleichung

[5-(5-bromo-2-fluoro-phenyl)-5-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester

trans-N,N′-dimethylcyclohexane-1,2-diamine

sodium azide

sodium-ascorbate

→

desired product

[5-(5-Amino-2-fluoro-phenyl)-5-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester

Lösungsmittel

EtOH

water

water

TBME

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe mixture was degassed
2. 2
   TemperaturThe mixture was cooled to rt
3. 3
   WaschenThe organic phase was washed with brine
4. 4
   Trocknendried with MgSO4.H2O
5. 5
   workup.ADDITIONThe crude product, consisting of a mixture of aryl azide and aniline
6. 6
   workup.DISSOLUTIONwas dissolved in 3 ml EtOH
7. 7
   workup.ADDITION3 ml THF and treated with 20 mg 10% Pd—C
8. 8
   Sonstigehad been consumed
9. 9
   workup.ADDITIONThe mixture was diluted with DCM
10. 10
    Filtrationfiltered over celite
11. 11
    SonstigeThe product was purified by chromatography on silica gel (heptane/30% EtOAc)

Vorschrift

To a solution of 0.69 g (1.703 mmol) [5-(5-bromo-2-fluoro-phenyl)-5-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester and 72.7 mg (0.511 mmol) trans-N,N′-dimethylcyclohexane-1,2-diamine in 7.5 ml EtOH was added a solution of 443 mg (6.81 mmol) sodium azide and 67.5 g (0.341 mmol) sodium-ascorbate in 3 ml water. The mixture was degassed and brought under nitrogen atmosphere. CuI (64.9 mg, 0.341 mmol) was added and the mixture was heated at 70° C. The initially formed suspension turned into a homogeneous blue solution. The mixture was cooled to rt, diluted with water and TBME. The organic phase was washed with brine and dried with MgSO4.H2O. The crude product, consisting of a mixture of aryl azide and aniline, was dissolved in 3 ml EtOH and 3 ml THF and treated with 20 mg 10% Pd—C and stirred under an atmosphere of hydrogen until all azide had been consumed. The mixture was diluted with DCM and filtered over celite. The product was purified by chromatography on silica gel (heptane/30% EtOAc) to give the desired product as colorless foam.

Quelle