tert-Butanol → Benzo[b]thiophene-7-acetonitrile

Add Benzo[b]thiophene-7-carboxaldehyde (2.34 g, 14.4 mmol) and lithium cyanide tetrahydrofuran complex (LiCN*1.5 Tetrahydrofuran, 204 mg, 1.44 mmol) to tetrahydrofuran (40 mL) under nitrogen. Add dropwise neat diethyl cyanophosphonate (2.8 mL, 18.4 mmol) to the stirring reaction mixture. Stir at room temp under nitrogen for 60 hours. Add 2-methyl-2-propanol (1.4 mL, 14.6 mmol). Add the reaction mixture via cannula to a stirred 0.1 molar solution of samarium(II) iodide in tetrahydrofuran (360 mL, 36.0 mmol) at 25° C. under nitrogen. If the resulting reaction mixture is not deep blue add additional samarium(II) iodide solution until deep blue color persists. Stir the reaction at 25° C. for 1 hour. Concentrate under reduced pressure, dilute with ethyl acetate, diethyl ether (1:1), wash with aqueous 0.1 M hydrochloric acid, and aqueous saturated sodium chloride. Dry the organic phase over anhydrous magnesium sulfate, filter, and concentrate under reduced pressure. Chromatograph on flash silica using a gradient from neat hexane to 25% ethyl acetate in hexane to obtain the title compound as an off-white solid.

1. customto the stirring reaction mixture
2. customIf the resulting reaction mixture
3. stirringStir
4. customthe reaction at 25° C. for 1 hour
5. concentrationConcentrate under reduced pressure
6. additiondilute with ethyl acetate, diethyl ether (1:1)
7. washwash with aqueous 0.1 M hydrochloric acid, and aqueous saturated sodium chloride
8. dry with materialDry the organic phase over anhydrous magnesium sulfate
9. filtrationfilter
10. concentrationconcentrate under reduced pressure

ORD record

ord-0915d12a70bb4f9c900e53642c249424

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08058425B2