1,2-Dimethoxyethane → tert-Butyl 4-(furan-3-yl)-3,6-dihydropyridine-1(2H)-carboxylate

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Reaction Steps

A flask was charged with boronic acid 3 (6.22 g, 55.6 mmol), triflate 2 (55.27 g, 166.8 mmol, 3 eq.), lithium chloride (7.07 g, 166.8 mmol, 3 eq.), aqueous 2N Na2CO3 (56 mL), 1,2-dimethoxyethane (120 mL) and Pd(PPh3)4 (3.21 g, 2.8 mmol, 0.05 eq.). The reaction mixture was heated to reflux under inert atmosphere for 4 h. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The resulting residue was partitioned between dichloromethane (150 mL), aqueous 2N Na2CO3 (125 mL), and concentrated ammonium hydroxide (9 mL). The layers were separated and the aqueous layer extracted again with dichloromethane (3×125 mL). The combined organics were dried over anhydrous magnesium sulfate and concentrated in vacuo. The resulting residue was purified via flash column chromatography (hexanes/CH2Cl2/EtOAc 9:1:1) to yield 4 as a light yellow oil (8.13 g, 59%). TLC Rf=0.43; 400 MHz 1H-NMR (CDCl3) δ 1.48 (s, 9H), 2.37 (s, 2H), 3.60 (t, J=3.6 Hz, 2H), 4.03 (s, 2H), 5.87 (s, 1H), 6.51 (s, 1H), 7.38 (d, J=6.8 Hz, 2H); 125 MHz 13C-NMR (CDCl3) δ 26.9, 39.5 (broad), 40.8 (broad), 43.6 (broad), 79.7, 107.2, 118.7 (broad), 126.8, 138.1, 143.5, 154.9. HRMS Calcd. for C14H19NO3Na [M++Na]: 272.1263. Found: 272.1271.

Provenance & Evidence