Reaction #45768

Reaction equation

Ethyl 3-bromopyruvate

4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-2-carbothioamide

sodium hydrogencarbonate

p-toluenesulfonic acid monohydrate

→

compound

Yield 91.3%

Ethyl 2-(4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazol-2-yl)-1,3-thiazole-4-carboxylate

Yield 91.3%

Solvents

toluene

water

Conditions

Workup

1. 1
   Temperatureby heating
2. 2
   TemperatureAfter cooling to room temperature
3. 3
   Temperatureby heating
4. 4
   Temperatureunder reflux in an oil bath at 125° C. for 15 hours
5. 5
   TemperatureAfter cooling to room temperature
6. 6
   Extractionfollowed by extraction with ethyl acetate (50 ml×2)
7. 7
   WashThe organic layer was washed with an aqueous saturated sodium hydrogencarbonate solution (50 ml) and saturated brine (50 ml)
8. 8
   Dryingdried over anhydrous sodium sulfate
9. 9
   ConcentrationAfter concentration
10. 10
    Otherthe resulting residue was purified by silica gel column chromatography (eluent, chloroform:ethyl acetate=100:1→25:1)

Procedure

Ethyl 3-bromopyruvate (72.2 μl, 0.518 mmol) was added to a toluene (10 ml) solution of 4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-2-carbothioamide (I-196-1) (124 mg, 0.398 mmol), followed by heating under reflux in an oil bath at 125° C. for 2 hours. After cooling to room temperature, p-toluenesulfonic acid monohydrate (15.2 mg, 0.080 mmol) was added to the reaction liquid, followed by heating under reflux in an oil bath at 125° C. for 15 hours. After cooling to room temperature, an aqueous saturated sodium hydrogencarbonate solution (50 ml) and water (50 ml) were added, followed by extraction with ethyl acetate (50 ml×2). The organic layer was washed with an aqueous saturated sodium hydrogencarbonate solution (50 ml) and saturated brine (50 ml), and dried over anhydrous sodium sulfate. After concentration, the resulting residue was purified by silica gel column chromatography (eluent, chloroform:ethyl acetate=100:1→25:1) to obtain the entitled compound (148 mg, 91.2%) as a pale yellow solid.

Source