Reaction #45696

Reaction equation

2-Chloro-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-cabonitrile

diisopropylethylamine

3-hydroxy-1-azetidine hydrochloride

→

7-Fluoro-2-(3-hydroxyazetidin-1-yl)-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile

Solvents

methylene chloride

Conditions

Workup

1. 1
   Temperatureby heating
2. 2
   Temperatureunder reflux in a sealed tube under nitrogen atmosphere for 6 hours
3. 3
   TemperatureAfter cooling
4. 4
   Washdilution with methylene chloride and washing with water and saturated brine
5. 5
   Dryingthe organic layer was dried over anhydrous sodium sulfate
6. 6
   Otherthe solvent was evaporated away under reduced pressure
7. 7
   OtherThe resisting residue was recrystallized
8. 8
   Otherpurified with n-hexane/ethyl acetate
9. 9
   Otherto obtain the entitled compound (123 mg, quant) as a yellow white solid

Procedure

2-Chloro-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-cabonitrile (I-130) (100 mg, 0.35 mmol) was dissolved in methylene chloride (2 ml), then diisopropylethylamine (237 μl, 1.39 mmol) and 3-hydroxy-1-azetidine hydrochloride (76 mg, 0.70 mmol) were added, followed by heating under reflux in a sealed tube under nitrogen atmosphere for 6 hours. After cooling, dilution with methylene chloride and washing with water and saturated brine, the organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated away under reduced pressure. The resisting residue was recrystallized and purified with n-hexane/ethyl acetate to obtain the entitled compound (123 mg, quant) as a yellow white solid.

Source