N-tert-butyl-2,6-dichloroisonicotinamide synthesis

Yield:1152504-12-5 93%

Reaction Conditions:

with trimethylaluminum in hexanes;toluene at 0 - 110;

Steps:

7.F

To toluene (48 ml.) at 0 ⁰C is added a solution of Me₃AI (19 ml. of 2.0 M in hexanes, 38.8 mmol), followed by dropwise addition of te/f-butylamine (4.1 ml_, 38.8 mmol). The reaction is warmed to rt before 2,6-dichloro-4-methoxycarbonylpyridine (1.0 g, 4.8 mmol) is added. The reaction is heated to 110 ⁰C for 2 h, cooled to 0 ⁰C, and quenched by the slow addition of 1 N HCI. After addition of 30 ml. of 1 N NaOH, the reaction is extracted three times with CH₂CI₂. The combined organic phases are washed with brine, dried (Na₂SO₄), and concentrated in vacuo. The residue is purified by flash chromatography (5 to 30% EtOAc/heptanes) to yield 1.1 g (93%) as a white solid: ¹H NMR (400 MHz, CDCI₃) δ ppm 1.46 (s, 9 H), 5.83 (s, 1 H), 7.51 (s, 2 H).

References:

WO2009/150230,2009,A1 Location in patent:Page/Page column 80-81