Hydrochloric Acid → HCID 66731958, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 2-chloroisonicotinate (4 g, 23.31 mmol) and Pd(PPh3)4 (0.539 g, 0.47 mmol) in tetrahydrofuran (120 mL) under nitrogen in a dried flask was added a freshly prepared solution of (3,5-di-tert-butylbenzyl)zinc(II) bromide (11.08 g, 31.78 mmol) in tetrahydrofuran (46 mL). The resulting bright yellow solution was heated to 60° C. for 35 min, then stirred at room temperature for 1 h. The reaction was quenched by addition of methanol (50 mL). The solution was diluted with EtOAc and washed with NH4Cl. The organic layer was dried over MgSO4, filtered and evaporated to yield a brown oil. The crude was redissolved in MTBE (180 mL) and solids were filtered off. Hydrogen chloride (4 M in dioxane, 6.42 mL, 25.66 mmol) was added dropwise during stirring and a suspension was formed. The suspension was stirred at room temperature for 10 min. The solid was collected by filtration and washed with MTBE. Redissolved in MTBE/satd NaHCO3. The phases were separated, the organic phase dried over Na2SO4, filtered and evaporated to yield methyl 2-(3,5-di-tert-butylbenzyl)isonicotinate (7.132 g, 90%) as a brown oil. 1H NMR (600 MHz, cdcl3) δ 1.28 (s, 18H), 3.89 (s, 3H), 4.19 (s, 2H), 7.11 (d, 2H), 7.27 (t, 1H), 7.64 (dd, 1H), 7.71 (s, 1H), 8.68 (d, 1H). MS m/z 340 (M+H)+

Provenance & Evidence