Acetonitrile → 3-Cyclobutyl-3-oxopropanenitrile

To 800 mL of THF at −78° C. was added n-BuLi (312.0 mL, 780.0 mmol, 2.5 M in hexanes). After the reaction temperature equilibrated (˜15 min), a solution of acetonitrile (40.7 mL, 780.0 mmol in 100 mL of THF) was added dropwise via an addition funnel over a 20 min period. The resulting milky white slurry was allowed to stir for 1 hr before a solution of ethyl cyclobutanecarboxylate (53.9 mL, 390.1 mmol in 150 mL of THF) was added down the side of the flask over a 20 min period. After one hr, the reaction was warmed to −45° C. (acetonitrile/CO2) and allowed to stir for two hr. The reaction was quenched cold by the dropwise addition of 2 N HCl (˜390 mL), pH=7 and then diluted with EtOAc (1 L). The layers were separated and the aqueous layer was extracted with CH2Cl2 (2×600 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to yield 3-cyclobutyl-3-oxo-propionitrile (quantitative yield) as a yellow oil that was used without further purification. Rf 0.32 (40% EtOAc/hexanes). m/z (APCI+) 138 (M−1).

1. custom(˜15 min)
2. additionwas added down the side of the flask over a 20 min period
3. customThe reaction was quenched cold by the dropwise addition of 2 N HCl (˜390 mL), pH=7
4. additiondiluted with EtOAc (1 L)
5. customThe layers were separated
6. extractionthe aqueous layer was extracted with CH2Cl2 (2×600 mL)
7. dry with materialThe combined organic layers were dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure

ORD record

ord-521a7849437542d68e6318786227030a

Source dataset

uspto-grants-2007_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07300944B2