86770-80-1

The general procedure for the synthesis of 3,3-difluorocyclobutanecarbonitrile from 3-oxocyclobutanecarbonitrile was as follows: Example 125A (8.21 g, 86 mmol) was dissolved in dichloromethane (135 mL), stirred and cooled to <10 °C at room temperature. DAST (11.41 mL, 86 mmol) was slowly added, followed by warming the reaction mixture to room temperature. Stirring was continued at room temperature for 2 hours. Upon completion of the reaction, the mixture was poured into saturated aqueous NaHCO3 solution (200 mL) for quenching and partitioning. The aqueous phase was extracted with dichloromethane (2 x 50 mL). The organic phases were combined, dried over anhydrous Na2SO4, filtered and concentrated to give Example 125B (9.14 g, 78 mmol, 90% yield) as a brown oil. The product was characterized by XH NMR (400 MHz, CDC13) with chemical shifts of 3.06-2.91 (m, 5H).

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