Reaction equation
[NH:1]=[N+:2]=[N-:3].[F:4][C:5]1[CH:6]=[C:7]([C:12](O)([CH3:14])[CH3:13])[CH:8]=[C:9]([F:11])[CH:10]=1.C(O)(C(F)(F)F)=O.[OH-].[Na+]>C(Cl)(Cl)Cl>[N:1]([C:12]([C:7]1[CH:8]=[C:9]([F:11])[CH:10]=[C:5]([F:4])[CH:6]=1)([CH3:14])[CH3:13])=[N+:2]=[N-:3]Participants
Conditions
- Temperature
- -5 °C
Procedure
Hydrogen azide (2M in toluene, 1.5 mol) was added to the solution of 2-(3,5-difluoro-phenyl)-propan-2-ol (Preparation 50, 145 g, 0.84 mol, 1 eq) in chloroform (1 L) and the content of the flask was cooled to −5° C. The mixture of TFA (2.5 mol, 2.98 eq) with chloroform (1:1) was added dropwise at such a rate to keep the internal temperature below −5° C. After the addition was complete, the reaction mixture was allowed to warm to room temperature and stirring was continued for 20 h. The reaction was poured into 2M sodium hydroxide and layers were separated. The aqueous phase was extracted two times with chloroform and combined organic extracts were washed with brine and dried over anhydrous magnesium sulfate. After removal of the solvent, the title compound was used in the next step without further purification (171 g, 0.87 mol, 100%).
Workup
- additionwas added dropwise at such a rate
- customthe internal temperature below −5° C
- additionAfter the addition
- temperatureto warm to room temperature
- customwere separated
- extractionThe aqueous phase was extracted two times with chloroform
- washwere washed with brine
- dry with materialdried over anhydrous magnesium sulfate
- customAfter removal of the solvent
- customthe title compound was used in the next step without further purification (171 g, 0.87 mol, 100%)
Sources & evidence
- ORD record
- ord-c707ead22b7345c08a5019d8b7e68bc3
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08357711B2
Linked notes
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