Synthesis
Example 37b Synthesis of 3-oxocyclobutanecarbonitrile: Sodium meta-periodate (284 g, 1.32 mol) was added in small batches (over 30-45 min) to 3-methylenecyclobutanecarbonitrile (30 g, 370 mmol) and ruthenium trichloride monohydrate (2.2 mol%, 1.5 g, 7.23 mmol) at 5 °C in a DCM-MeCN-water ( 645mL:645mL:945mL) in a solvent mixture. The reaction mixture was stirred vigorously at room temperature. Subsequently, the organic phase was separated and the aqueous phase was extracted with DCM (3 x 1500 mL). The combined organic extracts were filtered through a small pad of fast silica gel, and the silica gel pad was washed with 2000 mL of DCM. The filtrate was dried over MgSO4, filtered and concentrated under reduced pressure to give 3-oxocyclobutanecarbonitrile (28 g, 100%). The product was characterized by 1H NMR (400 MHz, CDCl3): δ 3.27 (quin, 1H), 3.57 (d, 4H).
References
[1] Patent: US2012/122843, 2012, A1. Location in patent: Page/Page column 39
[2] Patent: WO2015/179190, 2015, A1. Location in patent: Paragraph 0331
[3] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 13, p. 3947 - 3953
[4] Patent: US2014/80803, 2014, A1. Location in patent: Paragraph 1262
[5] Journal of Medicinal Chemistry, 2016, vol. 59, # 10, p. 4926 - 4947
