Reaction Steps
(189) A solution of 2-(oxazol-5-yl)pyridine (111 mg, 0.76 mmol) in anhydrous THF (5 mL) cooled to −75° C. under N2 was treated with n-BuLi (2.5 M in hexanes, 1.1 equiv, 0.84 mmol, 0.33 mL), and stirred for 20 min. ZnCl2 (0.5 M in THF, 2.0 equiv, 1.52 mmol, 3.0 mL) was added at −75° C., and stirred for 45 min at 0° C. Cul (1.0 equiv, 0.76 mmol, 145 mg) was added, and the solution was stirred for 10 min at 0° C. A separate flask was charged with octanoic acid (2 equiv, 1.52 mmol, 219 mg, 0.24 mL) in anhydrous CH2Cl2 (4.2 mL), and to this solution cooled to 0° C. under N2 was added oxalyl chloride (5 equiv, 7.6 mmol, 0.96 g, 0.66 mL). After stirring at rt for 2 h, the solution was concentrated under reduced pressure and dissolved in anhydrous THF (1.5 mL). The solution of octanoyl chloride was added and the solution was stirred for 1 h at 0° C. The reaction was diluted with EtOAc (10 mL), and washed with 15% aqueous NH4OH (1×10 mL), H2O (1×10 mL), and saturated aqueous NaCl (1×10 mL). The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure. Flash chromatography (SiO2, 2.5 cm×17.5 cm, 20% EtOAc-hexanes) afforded 1-(5-(pyridin-2-yl)oxazol-2-yl)octan-1-one (189) (107 mg, 0.39 mmol, 52% yield) as a light brown powder: mp 56° C; 1H NMR (CDCl3, 250 MHz) d 8.63 (br d, J=4.8 Hz, 1H), 7.85-7.74 (m, 3H), 7.28 (br t, J=5.1 Hz, 1H), 3.08 (t, J=7.3 Hz, 2H), 1.84-1.67 (m, 2H), 1.47-1.17 (m, 8H), 0.85 (br t, J=6.6 Hz, 3H); 13C NMR (CDCl3, 62.5 MHz) d 188.5, 157.3, 153.1, 150.0, 146.2, 137.0, 127.8, 124.1, 120.3, 39.1, 31.6, 29.0, 28.9, 24.0, 22.5, 14.0; IR (KBr) umax 2926, 2849, 1694, 1601, 1499, 1470, 1426, 1382 cm−1; MALDI-FTMS (DHB) m/z 273.1595 (C16H20N2O2+H+ requires 273.1597).
