Dimethyl Sulfate → 3-Methylisonicotinonitrile

Temperature

0 °C

To a cooled (0° C.) round bottom flask charged with 3-picoline-N-oxide (4.53 g, 42 mmol) was added dimethylsulfate (5.8 g, 47 mmol). The mixture was stirred for 18 hours and allowed to warm to room temperature. To this mixture was added potassium cyanide (3.25 g, 50 mmol) dissolved in ethyl alcohol/water (75 mL, 1:1). The reaction was stirred at room temperature for 18 hours, concentrated to half the volume and diluted with chloroform (100 mL). The organic layer was separated and washed with sodium chloride (sat. 25 mL) and dried over Na2SO4. The solvent was removed and the residual material was chromatographed (SiO2, hexanes/ethyl acetate) to give the title compound as off-white crystals (2.01 g, 41%). 1H NMR (300 MHz, DMSO-d6): δ 2.55 (s, 3H); 7.47 (d, 1H); J=5.1 Hz); 8.60 (d, 1H, J=5.1 Hz); 8.68 (s, 1H).

1. temperatureto warm to room temperature
2. stirringThe reaction was stirred at room temperature for 18 hours
3. concentrationconcentrated to half the volume
4. additiondiluted with chloroform (100 mL)
5. customThe organic layer was separated
6. washwashed with sodium chloride (sat. 25 mL)
7. dry with materialdried over Na2SO4
8. customThe solvent was removed
9. customthe residual material was chromatographed (SiO2, hexanes/ethyl acetate)

ORD record

ord-81cc55057a3148b39f0141875effb12a

Source dataset

uspto-grants-2005_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06946463B2