Reaction #475679

Reaction equation

Potassium tert-butoxide

tetrahydrofuran

4-amino-3-fluorophenol

4-chloropyridine-2-carboxamide

→

title compound

Yield 91.2%

4-(4-Amino-3-fluorophenoxy)pyridine

Yield 91.2%

Solvents

water

dimethyl sulfoxide

dimethyl sulfoxide

Conditions

Workup

1. 1
   Temperaturecooling on ice
2. 2
   workup.STIRRINGThe reaction mixture was stirred at room temperature for 30 minutes
3. 3
   workup.STIRRINGthe reaction mixture was stirred for 2 hours
4. 4
   FiltrationThe precipitated solid was collected by filtration
5. 5
   Washwashed with water (500 ml
6. 6
   workup.STIRRINGstirred for 30 minutes
7. 7
   Filtrationcollected by filtration again
8. 8
   Washwashed with water (500 ml
9. 9
   OtherDrying by hot air at 60° C.

Procedure

Potassium tert-butoxide (214 g) was dissolved in dimethyl sulfoxide (750 ml) and tetrahydrofuran (250 ml) under a nitrogen stream, and a solution of 4-amino-3-fluorophenol ½ naphthalene-2,6-disulfonate (242 g) and 4-chloropyridine-2-carboxamide (100 g) in dimethyl sulfoxide (1000 ml) was added dropwise to the solution with stirring and cooling on ice. The reaction mixture was stirred at room temperature for 30 minutes, then in an oil bath at 90° C. (external temperature) for 2 hours. The reaction mixture was allowed to cool down to room temperature, and water (3000 ml) was added, and the reaction mixture was stirred for 2 hours. The precipitated solid was collected by filtration, and washed with water (500 ml, twice). The residue was suspended in water (2000 ml), stirred for 30 minutes, collected by filtration again, and washed with water (500 ml, twice). Drying by hot air at 60° C. gave the title compound (119 g, 75.3%).

Source