62455-70-3

4630-82-4

75-05-8

62455-70-3

Procedure for the synthesis of 3-cyclohexyl-3-oxopropionitrile (JM18): anhydrous tetrahydrofuran (80 mL) was added to a dry round-bottomed flask fitted with a large stirring magnet under argon protection and the mixture was cooled to -78 °C. Subsequently, a hexane solution of 2.5 M n-butyllithium (32 mL, 80 mmol) was slowly added and the reaction was stirred for 5 min. Over 5 minutes, anhydrous acetonitrile (4.23 mL, 80 mmol) was added dropwise and stirring was continued at -78 °C for 90 minutes. Next, methyl cyclohexanecarboxylate (5.72 mL, 40 mmol) was added dropwise over 15 minutes and the reaction was stirred at -78 °C for another 2 hours. After that, the reaction mixture was allowed to slowly warm up to room temperature and stirring was continued for 30 minutes. Upon completion of the reaction, the reaction was quenched with 100 mL of water and stirred until all solids were completely dissolved. The aqueous layer was washed with ether (2 x 100 mL), and then the pH of the aqueous layer was adjusted to 3.0 by slow dropwise addition of hydrochloric acid, at which point the formation of a product precipitate was seen. The product was extracted from the aqueous solution with ether (3×100 mL), the organic layers were combined, dried with anhydrous magnesium sulfate, filtered and the solvent was evaporated under reduced pressure to give 5.3 g (87.6% yield) of a viscous yellow oil. The purity of the product met the requirements of the subsequent reaction.LCMS analysis results (retention time = 1.36 min): 151.2 (100%), 152.2 (12%), 153.2 (3%).