Reaction #45595

Reaction equation

4-amino-5-cyano-2-fluoro-6-methylbiphenyl-3-yl 3-benzyloxy-2,2-dimethylpropionate

p-toluenesulfonic acid monohydrate

toluene

→

compound

Yield 90.1%

2-(2-Benzyloxy-1,1-dimethylethyl)-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile

Yield 90.1%

Solvents

ethyl acetate

Conditions

Workup

1. 1
   Temperaturewas heated
2. 2
   Temperatureunder reflux for 3 hours
3. 3
   TemperatureAfter cooling
4. 4
   Otherthe reaction liquid
5. 5
   Washsuccessively washed with an aqueous saturated sodium hydrogencarbonate solution and saturated brine
6. 6
   Dryingdried on anhydrous magnesium sulfate
7. 7
   Otherthe solvent was evaporated away
8. 8
   Otherto obtain a pale brown residue
9. 9
   OtherThe resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=20:1→10:1)

Procedure

A mixture of 4-amino-5-cyano-2-fluoro-6-methylbiphenyl-3-yl 3-benzyloxy-2,2-dimethylpropionate (I-64) (390 mg, 0.902 mmol), p-toluenesulfonic acid monohydrate (17 mg, 0.09 mmol) and toluene (16 ml) was heated under reflux for 3 hours. After cooling, the reaction liquid was diluted with ethyl acetate, successively washed with an aqueous saturated sodium hydrogencarbonate solution and saturated brine, dried on anhydrous magnesium sulfate, then the solvent was evaporated away to obtain a pale brown residue. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=20:1→10:1) to obtain the entitled compound (337 mg, 90%) as a colorless oil.

Source