||With lithium aluminium tetrahydride; In tetrahydrofuran; diethyl ether; at 20℃; for 21.5h;Cooling with ice;
||To a cooled (ice water bath) suspension of <strong>[65515-39-1]2-methoxy-4,6-dimethylnicotinonitrile</strong> (50 g, 308 mmol) in Et20 (1000 mL) was added dropwise 2 M LiA1H4 in THF (308 mL,617 mmol) over 30 mm. The reaction was stirred for 60 mm, at which time the ice bath was removed. The reaction mixture was stirred at r.t. for 20 h. The reaction mixture was re-cooled (ice water bath) and quenched dropwise with H20 (25 mL), followed by 3 M NaOH (25 mL) and more H20 (75 mL). The cooling bath was removed and MgSO4 (10 heaping scoops) was added. The mixture was stirred for 1 h, at which time it was filteredthrough Celite. The solids were washed with Et20 and the mother liquors were concentrated. The residue was dried under vacuum (hivac) for 2 h to give (2-methoxy-4,6- dimethylpyridin-3-yl)methanamine (50 g, 98% yield) as a yellow oil which solidified upon freezing. MS(ES) [M+H] 167.0.
||With lithium aluminium tetrahydride; In diethyl ether; at 20℃; for 1h;
||Example 8: (2-Methoxy-4,6-dimethylpyridin-3-yl)methanamine To a slurry solution of aluminum (III) lithium hydride (234 mg, 6.17 mmol) in diethyl ether (2 ml_) was added a saturated solution of 2-methoxy-4,6- dimethylnicotinonitrile (500 mg, 3.08 mmol) in ether (5 ml_) and stirred at room temperature for 1 h. After completion of the reaction, minimum amount of water was carefully added and the crude product obtained was extracted with hot benzene / toluene and concentrated. Resulting oily compound was distilled at 0.5 mm vacuum at 95-100 SC to obtain the title compound. Yield: 300 mg (58.66 %); 1H NMR (DMSO-d6, 300 MHz): delta 6.53 (s, 1 H), 3.92 (s, 3H), 3.76 (s, 2H), 2.36 (s, 3H), 2.27 (s, 3H); MS (ESI+): m/z 166.9 [M+H]+.
||With lithium aluminium tetrahydride; tert-butyl methyl ether; In tetrahydrofuran; at 20℃; for 1h;
||LiAlH4 (48.0 g, 1.27 mol) was added into MTBE (600 mL) portion-wise at room temperature. To the suspension was added <strong>[65515-39-1]2-methoxy-4,6-dimethylpyridine-3-carbonitrile</strong> (Cpd S, 103 g, 0.636 mol) in MTBE/THF (1:1, 600 mL) portion-wise. The reaction mixture was stirred at room temperature for an hour then quenched with water (75 mL). The precipitate was collected by filtration and the solids washed with THF (3*100 mL). The filtrate was concentrated under vacuum to give the 1-(2-methoxy-4,6-dimethylpyridin-3-yl)methanamine (Cpd T), which was used in the next step directly.