Reaction #45776

Reaction equation

citric acid

Triethylamine

cyclobutanecarbonyl chloride

2-amino-5-phenyl-4-fluoro-3-hydroxy-6-methylbenzonitrile

→

compound

Yield 85.0%

4-Amino-5-cyano-2-fluoro-6-methylbiphenyl-3-yl cyclobutanecarboxylate

Yield 85.0%

Solvents

acetonitrile

Conditions

Workup

1. 1
   Otherthe solvent was evaporated away under, reduced pressure
2. 2
   workup.ADDITIONEthyl acetate was added to the resulting residue
3. 3
   Washby washing with saturated brine
4. 4
   DryingThe organic layer was dried over anhydrous magnesium sulfate
5. 5
   Otherthe solvent was evaporated away under reduced pressure

Procedure

Under nitrogen atmosphere, 2-amino-5-phenyl-4-fluoro-3-hydroxy-6-methylbenzonitrile (I-41) (250 mg, 1.03 mmol) was dissolved in acetonitrile (0.10 ml), and cooled to 0° C. Triethylamine (244 μl, 1.75 mmol) and cyclobutanecarbonyl chloride (177 μl, 1.55 mmol) were dropwise added to the solution, followed by stirring at room temperature for 1 hour. 10% citric acid was added to the reaction liquid, and the solvent was evaporated away under, reduced pressure. Ethyl acetate was added to the resulting residue, followed by washing with saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated away under reduced pressure. The resulting residue was subjected to silica gel column chromatography, and the eluate with ethyl acetate/hexane (1:4, v/v) gave the entitled compound (283 mg, 85%) as a white solid.

Source