Cyclopropanecarbonitrile → 1-(Pyrazin-2-yl)cyclopropane-1-carbonitrile

Temperature

0 °C

A mixture of 2-fluoropyrazine (2.0 g, 20.4 mmol, 1 eq) and cyclopropanecarbonitrile (1.5 ml, 20.4 mmol, 1 eq) In a dry flask under an argon atmosphere were dissolved in dry toluene (50 ml). The solution was cooled to 0° C. and potassium bis(trimethylsilyl)amide (0.5 M in toluene, 40.9 ml, 20.45 mmol, 1 eq) was added slowly over 5 min via syringe. The black, opaque reaction mixture was allowed to warm to room temperature and stirred for 4 h. The reaction was diluted with water (200 ml) and ethyl acetate (200 ml), and the layers were separated. The aqueous layer was back extracted with ethyl acetate (2×100 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated to give a black oil. The crude was purified by silica gel (60-120) column chromatography using 20% ethyl acetate in hexane as eluent to give 0.25 g of the product as light a yellow oil. Yield: 0.25 g (8.4%). 1H NMR (400 MHz, CD3OD): δ 1.84-1.86 (m, 4H), 8.51-8.55 (q, 2H), 8.89 (s, 1H). LCMS: (ES+) m/z=146.2 (M)+

1. customThe black, opaque reaction mixture
2. temperatureto warm to room temperature
3. customthe layers were separated
4. extractionThe aqueous layer was back extracted with ethyl acetate (2×100 ml)
5. dry with materialThe combined organic layers were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customto give a black oil
9. customThe crude was purified by silica gel (60-120) column chromatography

ORD record

ord-0e8bce72c698409aaf0de7067755461a

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07994171B2