Acetonitrile → 3-(1-Methoxy-cyclopropyl)-3-oxo-propionitrile

Temperature

-78 °C

Add a solution of 2 M LDA in THF (29.1 mL, 58.3 mmol) to a dry ice-acetone cooled solution of 1-methoxy-cyclopropanecarboxylic acid methyl ester (WO2005/014577) (3.45 g, 26.5 mmol) and acetonitrile (2.17 g mL, 53.0 mmol) in THF (30 mL). Stir the reaction mixture at −78° C. for 1 hour and then at 22° C. for 0.5 hour. Evaporate the solvent to give a brown solid. Filter and wash with hexanes. Add 2N hydrochloric acid and extract three times with diethyl ether (50 mL each). Dry the combined organic phases over sodium sulfate. Removal of solvent provides a red oil (3.55 g, 96% yield, ES+(m/z) 140.1 [M+H]).

1. waitat 22° C. for 0.5 hour
2. customEvaporate the solvent
3. customto give a brown solid
4. filtrationFilter
5. washwash with hexanes
6. additionAdd 2N hydrochloric acid
7. extractionextract three times with diethyl ether (50 mL each)
8. dry with materialDry the combined organic phases over sodium sulfate
9. customRemoval of solvent
10. customprovides a red oil (3.55 g, 96% yield, ES+(m/z) 140.1 [M+H])

ORD record

ord-e01a5c8edbb4451cb6478d7d4eed9bc5

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07582638B2