Ammonia → 2-Ethyl-6-methylisonicotinonitrile

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, 3 H), 2.61 (s, 3 H), 2.86 (q, J=7.5 Hz, 2 H), 7.21 (s, 2H).

1. additionis added
2. stirringStirring
3. waitis continued for 2 h at rt before the solvent
4. customis evaporated under reduced pressure
5. dissolutionThe residue is dissolved in DCM (80 mL)
6. additionis added at 0° C
7. stirringThe mixture is stirred at rt for 2 h, before it
8. washwashed sat. aq. Na2CO3
9. dry with materialThe organic phase is dried over MgSO4
10. filtrationfiltered
11. customevaporated
12. customThe crude product is purified by CC on silica gel eluting with heptane:EA 4:1

ORD record

ord-6d2b2d23b81045218aa16705351eff28

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697732B2