Reaction #168728

Reaction equation

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

Solvents

EtOH

water

water

TBME

Conditions

Workup

1. 1
   OtherThe mixture was degassed
2. 2
   TemperatureThe mixture was cooled to rt
3. 3
   WashThe organic phase was washed with brine
4. 4
   Dryingdried with MgSO4.H2O
5. 5
   OtherThe crude product was purified by chromatography on silica gel (hexane/5-8% TBME)

Procedure

To a solution of 7.27 g (17.18 mmol) [5-(5-bromo-2-fluoro-phenyl)-5-difluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester and 2.443 g (17.18 mmol) trans-N,N′-dimethylcyclohexane-1,2-diamine in 237 ml EtOH was added a solution of 8.93 g (137 mmol) sodium azide and 1.361 g (6.87 mmol) sodium-ascorbate in 102 ml water. The mixture was degassed and brought under nitrogen atmosphere. CuI (1.309 g, 6.87 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 was purified by chromatography on silica gel (hexane/5-8% TBME) to give the desired product as a colorless solid.

Source