Ammonia → 2-Ethyl-6-methylisonicotinonitrile

Participants

Reaction Steps

To a solution of 2-ethyl-6-methyl-isonicotinic acid hydrochloride (1.85 g, 9.18 mmol, Example J) in DMF (90 mL), DIPEA (6.3 mL, 4.75 g, 36.7 mmol)) is added. The mixture is cooled to 0° C. before PyBOP (5.25 g, 10.1 mmol) is added. Stirring is continued at 0° C. for 15 min, then NH3 (64 mL of a 0.5 M solution in dioxane) is added. Stirring is continued for 2 h at rt before the solvent is evaporated under reduced pressure. The residue is dissolved in DCM (80 mL) and pyridine (4.5 mL, 4.39 g, 55.5 mmol) followed by TFA anhydride (6.32 mL, 9.39 g, 44.7 mmol) is added at 0° C. The mixture is stirred at rt for 2 h, before it is diluted with DCM, washed sat. aq. Na2CO3. The organic phase is dried over MgSO4, filtered and evaporated. The crude product is purified by CC on silica gel eluting with heptane:EA 4:1 to give 2-ethyl-6-methyl-isonicotinonitrile (0.675 g) as a yellow oil; 1H NMR (CDCl3): δ 1.33 (t, J=7.5 Hz, 3H), 2.61 (s, 3H), 2.86 (q, J=7.5 Hz, 2H), 7.21 (s, 2H).

Provenance & Evidence