2-(1-(ethylsulfonyl)azetidin-3-ylidene)acetonitrile

The Uses of 2-(1-(ethylsulfonyl)azetidin-3-ylidene)acetonitrile

2-(1-(Ethylsulfonyl)azetidin-3-ylidene)acetonitrile is an intermediate in the synthesis of Baricitinib, a JAK 1 and 2 inhibitor used in the treatment of rheumatoid arthritis.

Synthesis

2-(1-(ethylsulfonyl)azetidin-3-ylidene)acetonitrile is synthesized by first treating azetidine-3-ol hydrochloride with an equimolar equivalent of an alkanesulfonyl chloride, preferably ethanesulfonyl chloride, to give l-ethylsulfonylazetidin-3-ol. Preferably, the reaction is performed in a biphasic solution comprising a mixture of an organic phase and a aqueous phase, preferably THF with an aqueous solution which is basic, while maintaining the solution at room temperature or a temperature slightly below room temperature, preferably 20 °C. The reaction is followed to completion using standard monitoring techniques. Typically, the reaction is complete within 1 to 5 hours. The organic layer is removed, preferably by distillation, and the aqueous layer is extracted with an appropriate solvent such as toluene, p-cymene, and CPME. Preferably the extraction solvent is toluene. Alternatively, the toluene extractions can be excluded if recrystallization of 2-(1-(ethylsulfonyl)azetidin-3-ylidene)acetonitrile is performed.